Vertical transmission of microbiomes into embryo culture media and its association with assisted reproductive outcomes.

RESEARCH QUESTION: Can microbes vertically transmit from semen and follicular fluid to embryo culture media during assisted reproductive technology (ART) treatment? DESIGN: Spent embryo culture media (SECM), seminal fluid and follicular fluid samples were collected from 61 couples with infertility undergoing ART treatment at the Prince of Wales Hospital, Hong Kong SAR, China. Metagenomic analysis was conducted using 16s rRNA sequencing to identify the source of microbes in SECM, correlation between the semen microbiome and male infertility, and correlation between the follicular fluid microbiome and female infertility. RESULTS: Microbial vertical transmission into SECM was reported in 82.5% of cases, and semen was the main source of contamination in conventional IVF cases. The increased abundances of Staphylococcus spp. and Streptococcus anginosus in semen had negative impacts on total motility and sperm count, respectively (P < 0.001). Significant increases in abundance of the genera Prophyromonas, Neisseria and Facklamia were observed in follicular fluid in women with anovulation, uterine factor infertility and unexplained infertility, respectively (P < 0.01). No significant correlation was found between the bacteria identified in all sample types and ART outcomes, including fertilization rate, embryo development, number of available embryos, and clinical pregnancy rate. CONCLUSION: Embryo culture media can be contaminated during ART treatment, not only by seminal microbes but also by follicular fluid and other sources of microbes. Strong correlations were found between specific microbial taxa in semen and sperm quality, and between the follicular fluid microbiome and the aetiology of female infertility. However, no significant association was found between the microbiomes of SECM, semen and follicular fluid and ART outcomes.

Multilevel Factors Affecting Healthcare Workers' Perceived Stress and Risk of Infection During COVID-19 Pandemic.

Objectives: This study aimed to identify key factors affecting Healthcare workers (HCWs) perceived stress and risk of contracting COVID-19 among themselves and their family members during the pandemic. Methods: A cross-sectional online questionnaire study was conducted between 19 March and April 5, 2020 in Hong Kong. HCWs from public hospitals and private dentists, and their family members participated. Results: A total of 747 HCWs and 245 family members participated. Higher perceived stress in HCWs was associated with more negative changes in family relationship (p = 0.025). The HCWs' perceived stress, however, was positively associated with family cohesion (p = 0.033) and stress levels of family members (p < 0.001). The level of HCWs' satisfaction toward the hospital policies in response to the COVID-19 outbreak was associated with lower levels of perceived stress and risk of themselves or their family members contracting COVID-19. HCWs' previous frontline experience of SARS was significantly associated with less perceived risk of themselves or their family members contracting COVID-19. Conclusion: Hospital policies addressing HCWs' needs, frontline experience of SARS, and family relationship influenced psychological wellbeing of HCWs during the COVID-19 outbreak.

Common variants associated with changes in levels of circulating free fatty acids after administration of glucose-insulin-potassium (GIK) therapy in the IMMEDIATE trial.

Glucose-insulin-potassium (GIK) therapy may promote a shift from oxygen-wasteful free fatty acid (FFA) metabolism to glycolysis, potentially reducing myocardial damage during ischemia. Genetic variation associated with FFA response to GIK was investigated in an IMMEDIATE (Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care) sub-study (n=117). In patients with confirmed acute coronary syndromes, associations between 132 634 variants and 12-h circulating FFA response were assessed. Between initial and 6-h measurements, three LINGO2 variants were associated with increased levels of total FFA (P-value for 2 degree of freedom test, P2df ⩽5.51 × 10-7). Lead LINGO2 single-nucleotide polymorphism, rs12003487, was nominally associated with reduced 30-day ejection fraction (P2df=0.03). Several LINGO2 signals were linked to alterations in epigenetic profile and gene expression levels. Between 6 and 12 h, rs7017336 nearest to IMPA1/FABP12 showed an association with decreased saturated FFAs (P2df=5.47 × 10-7). Nearest to DUSP26, rs7464104 was associated with a decrease in unsaturated FFAs (P2df=5.51 × 10-7). Genetic variation may modify FFA response to GIK, potentially conferring less beneficial outcomes.

Genetic modifiers of response to glucose-insulin-potassium (GIK) infusion in acute coronary syndromes and associations with clinical outcomes in the IMMEDIATE trial.

Modifiers of response to glucose, insulin and potassium (GIK) infusion may affect clinical outcomes in acute coronary syndromes (ACS). In an Immediate Myocardial Metabolic Enhancement During Initial Assessment And Treatment In Emergency Care (IMMEDIATE) trial's sub-study (n = 318), we explored effects of 132,634 genetic variants on plasma glucose and potassium response to 12-h GIK infusion. Associations between metabolite-associated variants and infarct size (n = 84) were assessed. The 'G' allele of rs12641551, near ACSL1, as well as the 'A' allele of XPO4 rs2585897 were associated with a differential glucose response (P for 2 degrees of freedom test, P2df ⩽ 4.75 × 10(-7)) and infarct size with GIK (P2df < 0.05). Variants within or near TAS1R3, LCA5, DNAH5, PTPRG, MAGI1, PTCSC3, STRADA, AKAP12, ARFGEF2, ADCYAP1, SETX, NDRG4 and ABCB11 modified glucose response, and near CSF1/AHCYL1 potassium response (P2df ⩽ 4.26 × 10(-7)), but not outcomes. Gene variants may modify glucose and potassium response to GIK infusion, contributing to cardiovascular outcomes in ACS.

Genetic variation at glucose and insulin trait loci and response to glucose-insulin-potassium (GIK) therapy: the IMMEDIATE trial.

The mechanistic effects of intravenous glucose, insulin and potassium (GIK) in cardiac ischemia are not well understood. We conducted a genetic sub-study of the Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care (IMMEDIATE) Trial to explore effects of common and rare glucose and insulin-related genetic loci on initial to 6-h and 6- to 12-h change in plasma glucose and potassium. We identified 27 NOTCH2/ADAM30 and 8 C2CD4B variants conferring a 40-57% increase in glucose during the first 6 h of infusion (P<5.96 × 10(-6)). Significant associations were also found for ABCB11 and SLC30A8 single-nucleotide polymorphisms (SNPs) and glucose responses, and an SEC61A2 SNP with a potassium response to GIK. These studies identify genetic factors that may impact the metabolic response to GIK, which could influence treatment benefits in the setting of acute coronary syndromes (ACS).

Genetic variation in the renin-angiotensin-aldosterone system is associated with cardiovascular risk factors and early mortality in established coronary heart disease.

This study examined renin-angiotensin-aldosterone (RAAS) system gene variants for associations with cardiovascular risk factors and outcomes in coronary heart disease. Coronary disease patients (n=1186) were genotyped for 21 single-nucleotide polymorphisms (SNPs) within angiotensinogen (AGT), angiotensin-converting enzyme (ACE), angiotensin-II type-1 receptor (AGTR1) and aldosterone synthase (CYP11B2). Associations with all-cause mortality and cardiovascular readmissions were assessed over a median of 3.0 years. The AGT M235T 'T' allele was associated with a younger age of clinical coronary disease onset (P=0.006), and the AGT rs2478545 minor allele was associated with lower circulating natriuretic peptides (P=0.0001-P=0.001) and E/E(1) (P=0.018). Minor alleles of AGT SNPs rs1926723 and rs11122576 were associated with more frequent history of renal disease (P0.04) and type-2 diabetes (P0.02), higher body mass index (P0.02) and greater mortality (P0.007). AGT rs11568054 minor allele carriers had more frequent history of renal disease (P=0.04) and higher plasma creatinine (P=0.033). AGT rs6687360 minor allele carriers exhibited worse survival (P=0.02). ACE rs4267385 was associated with older clinical coronary disease onset (P=0.008) and hypertension (P=0.013) onset, increased plasma creatinine (P=0.01), yet greater mortality (P=0.044). Less history of hypertension was observed with the AGTR1 rs12685977 minor allele (P=0.039). Genetic variation within the RAAS was associated with cardiovascular risk factors and accordingly poorer survival.

PHF11 is not a major candidate gene for asthma or eczema in Chinese children.

SUMMARY: Positional cloning and candidate gene studies in different Caucasian populations identified the gene encoding plant homeodomain zinc finger protein 11 (PHF11) to be associated with asthma and eczema. Microarray analysis also confirmed increased PHF11 expression in type 1 T-helper lymphocytes. However, such disease associations are unclear in Asian subjects. This case-control genetic association study investigated the relationship between asthma and eczema phenotypes and tagging single-nucleotide polymorphisms (SNPs) of PHF11 in Hong Kong Chinese children. Three hundred and nineteen asthmatic children and 236 children with eczema were recruited from hospital clinics and 445 children without any history of allergic disease were recruited as controls from local schools and hospitals. Atopy was defined by the presence of allergen-specific IgE in plasma or positive skin prick tests with wheal >or=3 mm larger than negative control. Lung function of asthmatics was evaluated by pre-bronchodilator spirometry. Ten PHF11 SNPs were genotyped by multiplex SNaPshot assay. Genotyping call rates were 100% for all SNPs, which also followed Hardy-Weinberg equilibrium. These SNPs were tightly linked in one haplotype block (D' >or= 0.95 for nearly all SNP pairs). Physician-diagnosed asthma was weakly associated with PHF11 +20860 and +22818 (P = 0.032 for both). Atopy was also associated with PHF11 +22398 (P = 0.029). However, none of the PHF11 SNPs was associated with eczema diagnosis and plasma total IgE and spirometric parameters in our patients. Our findings do not support PHF11 to be a major candidate gene for asthma, eczema and aeroallergen sensitization in Chinese children.

Economic evaluation of universal infant vaccination with 7vPCV in Hong Kong.

OBJECTIVES: The purpose of this study was to evaluate the clinical and economic benefits of routine infant vaccination with seven-valent pneumococcal conjugate vaccine (7vPCV) in Hong Kong. METHODS: A decision-analytic model was populated with local age-specific incidence data to simulate the expected health outcomes resulting from 7vPCV vaccination of a birth cohort of 57,100 children compared with an unvaccinated cohort over a 10-year horizon. Primary analyses were conducted from a payer perspective, using local inpatient and outpatient costs associated with the treatment of pneumococcal disease. Vaccine efficacy rates were consistent with results from pivotal clinical trials. The reduction in adult invasive pneumococcal disease (IPD) and associated cost avoidance due to the indirect effect of vaccination were estimated in line with published overseas rates. RESULTS: Universal 7vPCV vaccination was estimated to prevent 524 cases of IPD and more than 2580 cases of otitis media in the birth cohort over a 10-year period, leading to a reduction of HK$28.7 million (US$3.7 million) in direct medical costs. Additional cost savings from the indirect prevention of 919 adult cases of IPD during this time period also resulted. Overall, 7vPCV vaccination was estimated to have an incremental cost per life-year gained of HK$50,456 (US$6460) from a payer perspective or HK$46,308 (US$5929) when both direct and indirect costs were included. CONCLUSION: With reference to the World Health Organization's threshold for cost-effectiveness, results from this study indicate that routine infant vaccination with 7vPCV is a cost-effective intervention because of the added cost savings resulting from the indirect effect of vaccination on adult disease.

Rapid control of norovirus gastroenteritis outbreak in an acute paediatric ward.

AIM: To provide a practical action plan for effective infection control of norovirus outbreak in acute paediatric wards. METHODS: We report the infection control measures that were implemented to terminate and to prevent nosocomial spread of norovirus gastroenteritis in an open-designed paediatric ward. RESULTS: Nine children, one visitor, and one medical student were affected in a norovirus gastroenteritis outbreak in an acute paediatric ward. Vomiting was the main presenting symptom. The outbreak was rapidly terminated three days after implementation of stringent infection control measures and there was no second wave of attack. These measures included strict contact precautions, prompt isolation and cohorting of symptomatic patients, vigorous environmental cleansing with concentrated disinfectant (hypochlorite solution 1000 ppm), meticulous handling of waste products, and efficient contact tracing of exposed patients, family members, and medical students. CONCLUSION: Prompt implementation of stringent infection control measures and contact tracing can rapidly terminate the norovirus outbreak and prevent a second wave of infection. Children with unexplained vomiting and those with contact history of gastroenteritis should be properly triaged, isolated, and investigated for possible infective causes, including norovirus-induced gastroenteritis.

Clinical, virologic and immunologic profiles of a young infant with severe acute respiratory syndrome.

The clinical findings, plasma viral load, cytokines and chemokines of a 4-month-old infant with severe acute respiratory syndrome (SARS) were assessed at different phases of the disease. Ribavirin failed to inhibit SARS coronavirus (SARS-CoV) replication. One-step real time reverse transcription-polymerase chain reaction for plasma SARS-CoV RNA quantification was useful for early diagnosis and monitoring viremia.

Hepatic failure in a child with anti-epileptic hypersensitivity syndrome.

An 11-year-old boy developed severe hypersensitivity reaction to phenobarbitone resulted in fulminant hepatic failure. During the course of illness, he developed clinical features compatible with severe acute respiratory syndrome (SARS) that may have complicated the recovery of his underlying hypersensitivity reaction, which was subsequently controlled with intravenous immune globulin and corticosteroids.

A randomized, single-blind and crossover study of an amino acid-based milk formula in treating young children with atopic dermatitis.

Cow's milk and soy protein allergies are commonly associated with atopic dermatitis (AD) in young children. Amino acid (AA)-based elemental milk formula may improve AD control in these patients. This study investigates the efficacy of AA-based formula in treating young AD patients irrespective of their food allergy status. AD patients younger than 3 yr old were eligible. Sensitization to food allergens was ascertained by skin prick tests and allergen-specific immunoglobulin E (IgE) assay. Patients were then randomly allocated to take either active treatment or pre-existing formulae (placebo) for 6 wk. They were allowed a 6-wk washout period before crossed over to the other intervention for another 6 wk. Fifteen AD patients, with median (interquartile range, IQR) age of 1.4 (0.6-2.6) yr, were recruited. Their median (IQR) SCORAD score was 23.9 (10.5-29.7). Seven of them were sensitized to cow's milk or soybean. Among 11 patients who completed the study, the median changes for all scores and urinary eosinophil protein X (EPX) concentration were not statistically significant. There was also no evidence of carry-over effects for SCORAD and its various components and global health score, except for urinary EPX concentration (p = 0.05). Our results do not support the use of AA-based elemental milk formula in treating young children with AD irrespective of their food allergy status.

Laboratory diagnosis of SARS.

The virologic test results of 415 patients with severe acute respiratory syndrome (SARS) were examined. The peak detection rate for SARS-associated coronavirus occurred at week 2 after illness onset for respiratory specimens, at weeks 2 to 3 for stool or rectal swab specimens, and at week 4 for urine specimens. The latest stool sample that was positive by reverse transcription-polymerase chain reaction (RT-PCR) was collected on day 75 while the patient was receiving intensive care. Tracheal aspirate and stool samples had a higher diagnostic yield (RT-PCR average positive rate for first 2 weeks: 66.7% and 56.5%, respectively). Pooled throat and nasal swabs, rectal swab, nasal swab, throat swab, and nasopharyngeal aspirate specimens provided a moderate yield (29.7%-40.0%), whereas throat washing and urine specimens showed a lower yield (17.3% and 4.5%). The collection procedures for stool and pooled nasal and throat swab specimens were the least likely to transmit infection, and the combination gave the highest yield for coronavirus detection by RT-PCR. Positive virologic test results in patient groups were associated with mechanical ventilation or death (p < 0.001), suggesting a correlation between viral load and disease severity.

SARS in newborns and children.

The severe acute respiratory syndrome (SARS) is a highly contagious infection caused by a newly discovered strain of coronavirus (SARS-CoV). Infants born to pregnant women with SARS did not appear to acquire the infection through vertical transmission. Some newborn infants, however, developed severe intrauterine growth retardation and life-threatening gastrointestinal complications. It is now known that the clinical course and prognosis are different between paediatric and adult SARS patients. Young children (< 12 years), in general, run a less aggressive clinical course than do teenage and adult patients. Thus far, no fatalities have been reported in the paediatric age group (< or =18 years). This review describes the current understanding of the clinical manifestations, diagnostic tests, immunological profiles, patient management and outcomes of SARS-CoV infection in the paediatric population.

Inflammatory cytokine profile in children with severe acute respiratory syndrome.

OBJECTIVE: To study the inflammatory cytokine profile in children with severe acute respiratory syndrome (SARS) and to investigate whether monoclonal antibody to tumor necrosis factor-alpha (TNF-alpha) could be considered for treatment of these patients. METHODS: Plasma inflammatory cytokine concentrations (interleukin [IL]-1beta, IL-6, IL-8, IL-10, IL-12p70, and TNF-alpha) were monitored longitudinally on admission, immediately before corticosteroids, and 1 to 2 days and 7 to 10 days after the drug treatment in a cohort of pediatric patients (n = 8) with virologic confirmed SARS-associated coronavirus infection. None of the patients required mechanical ventilation or intensive care treatment. All children except 1 (patient 3) received corticosteroids. RESULTS: Plasma IL-1beta levels (excluding patient 3) were substantially elevated immediately before (range: 7-721 ng/L) and 7 to 10 days after (range: 7-664 ng/L) corticosteroid treatment. In contrast, the plasma concentrations of other key proinflammatory cytokines, including IL-6 and TNF-alpha, were not overtly increased in any of the patients throughout the course of illness. In addition, plasma IL-10 concentration was significantly lower 1 to 2 days and 7 to 10 days after corticosteroid treatment, compared with the immediate pretreatment level. Similarly, plasma IL-6 and IL-8 concentrations were significantly decreased 7 to 10 days after the drug treatment. CONCLUSIONS: Pediatric SARS patients have markedly elevated circulating IL-1beta levels, which suggests selective activation of the caspase-1-dependent pathway. Other key proinflammatory cytokines, IL-6 and TNF-alpha, showed only mildly elevated levels at the initial phase of the illness. The current evidence does not support the use of TNF-alpha monoclonal antibody in this group of children.

Severe acute respiratory syndrome (SARS): chest radiographic features in children.

BACKGROUND: Severe acute respiratory syndrome (SARS) is a recently recognized condition of viral origin associated with substantial morbidity and mortality rates in adults. Little information is available on its radiologic manifestations in children. OBJECTIVE: The goal of this study was to characterize the radiographic presentation of children with SARS. MATERIALS AND METHODS: We abstracted data (n=62) on the radiologic appearance and course of SARS in pediatric patients with suspect (n=25) or probable (n=37) SARS, diagnosed in five hospital sites located in three cities: Toronto, Singapore, and Hong Kong. Available chest radiographs and thoracic CTs were reviewed for the presence of the following radiographic findings: airspace disease, air bronchograms, airways inflammation and peribronchial thickening, interstitial disease, pleural effusion, and hilar adenopathy. RESULTS: A total of 62 patients (suspect=25, probable=37) were evaluated for SARS. Patient ages ranged from 5.5 months to 17 years and 11.5 months (average, 6 years and 10 months) with a female-to-male ratio of 32:30. Forty-one patients (66.1%) were in close contact with other probable, suspect, or quarantined cases; 10 patients (16.1%) had recently traveled to WHO-designated affected areas within 10 days; and 7 patients (11.2%) were transferred from other hospitals that had SARS patients. Three patients, who did not have close/hospital contact or travel history to affected areas, were classified as SARS cases based on their clinical signs and symptoms and on the fact that they were living in an endemic area. The most prominent clinical presentations were fever, with a temperature over 38 degrees C (100%), cough (62.9%), rhinorrhea (22.6%), myalgia (17.7%), chills (14.5%), and headache (11.3%). Other findings included sore throat (9.7%), gastrointestinal symptoms (9.7%), rigor (8.1%), and lethargy (6.5%). In general, fever and cough were the most common clinical presentations amongst younger pediatric SARS cases (age<10 years), whereas, in addition to these symptoms, headache, myalgia, sore throat, chills, and/or rigor were common in older patients (age>/=10 years). The chest radiographs of 35.5% of patients were normal. The most prominent radiological findings that were observed in the remaining patients were areas of consolidation (45.2%), often peripheral with multifocal lesions in 22.6%. Peribronchial thickening was noted on chest radiographs of 14.5% of patients. Pleural effusion was observed only in one patient (age 17 years and 11.5 months), whereas interstitial disease was not observed in any patient. CONCLUSION: In pediatric cases, SARS manifests with nonspecific radiographic features making radiological differentiation difficult, especially from other commonly encountered childhood respiratory viral illnesses causing airspace disease. The radiographic presentation of suspected SARS cases ranged from normal to mild perihilar peribronchial thickening. The radiographic presentations, as expected, were relatively more pronounced in the SARS probable cases.

Infants born to mothers with severe acute respiratory syndrome.

Severe acute respiratory syndrome (SARS) is a newly discovered infectious disease caused by a novel coronavirus. During the community outbreak in Hong Kong, 5 liveborn infants were born to pregnant women with SARS. A systematic search for perinatal transmission of the SARS-associated coronavirus, including serial reverse transcriptase-polymerase chain reaction assays, viral cultures, and paired serologic titers, failed to detect the virus in any of the infants. In addition, none of the infants developed clinical, radiologic, hematologic, or biochemical evidence suggestive of SARS. One preterm infant developed jejunal perforation and another developed necrotizing enterocolitis with ileal perforation shortly after birth. This case series is the first report to describe the clinical course of the first cohort of liveborn infants born to pregnant women with SARS.

Expression of ERRP in normal and neoplastic pancreata and its relationship to clinicopathologic parameters in pancreatic adenocarcinoma.

INTRODUCTION AND AIMS: Epidermal growth factor (EGF) and its receptor (EGFR) play crucial roles in cellular signaling in many malignancies, including pancreatic neoplasia. Attenuation of EGFR signaling has been considered novel strategy for the management of human malignancies in several ongoing clinical trials. We recently isolated a novel negative regulator of EGFR, termed EGF receptor related protein (ERRP), whose expression appears to attenuate EGFR activation. In the current study, the expression of ERRP in normal and neoplastic pancreas was investigated and correlated with the clinicopathologic parameters in pancreatic ductal adenocarcinoma (DA). METHODOLOGY: Using rabbit polyclonal antibody that specifically interacts with ERRP, immunohistochemical staining was performed on 45 benign pancreata and 106 cases of DA. The intensity and percentage of cells with cytoplasmic and membranous staining were scored as 0, 1, 2, or 3. A combined score was calculated as intensity x percent/3, and for comparative analysis, the data were arbitrarily divided into three groups: <20, 20-49, and > or =50. The expression of ERRP was correlated with patient age, gender, race, tumor size, stage, grade, and survival. RESULTS: ERRP was expressed in most benign ductal epithelium and islet cells, but not in normal acinar cells. In pancreatic ductal adenocarcinoma, ERRP expression frequency decreased progressively from well (WD) to moderate (MD) to poorly differentiated (PD) carcinoma (58%, 43%, and 15% respectively, < 0.001). ERRP expression was correlated with survival in DA showing decreased median survival with decreased ERRP score ( = 0.0035). Median survival of the lower intensity (0 or 1) group was less than that of the higher intensity (2 or 3) group (8 14 months, = 0.002). The higher expressing group (> or =50% of cells) had longer median survival (17 months) than the lower expressing (<50% of cells) group (10 months, = 0.003). Stepwise multiple regression analyses revealed that ERRP expression score and tumor grade are the significant predictors of survival in pancreatic ductal carcinomas ( < 0.03). CONCLUSION: ERRP is usually expressed in benign ductal epithelium, but not in ductal adenocarcinoma. Its expression decreases with decreasing tumor differentiation. Low levels of ERRP are associated with poor clinical outcome, suggesting that progressive loss of ERRP, a negative regulator of EGFR, may partly stimulate aggressive tumor cell growth in pancreatic adenocarcinoma.

Pharmacologic management of movement disorder after midbrain haemorrhage.

Movement disorders following midbrain haemorrhage are infrequently encountered in rehabilitation, and are uncommonly corrected by pharmacologic means. This report describes a 20 year-old male with a prior history of cocaine abuse who presented with a 4 day history of dysarthria and blurred vision following methamphetamine abuse. Physical examination demonstrated hypertension, left facial hemispasm, bilateral upward gaze paresis and ataxic gait. Magnetic resonance imaging/magnetic resonance angiography (MRI/MRA) showed multifocal parenchymal haematomas in the mesencephalic tegmentum, subcortical left front region and right anterior thalamus consistent with cavernous angiomas. The patient was transferred to rehabilitation on hospital day 5. The following day, he developed choreoathetoid movements, dystonia, and aphasia, secondary to an extension of the midbrain haemorrhage. Cogentin was initiated with slight improvement in choreoathetoid movements. The patient began intensive multidisciplinary rehabilitation therapy but after 18 days of therapy, the patient remained totally dependent in activities of daily living (ADLs), transfers, mobility and was unable to communicate in any manner. A trial of Sinemet was initiated, with resultant steady improvement in functional ability over the next month. By discharge, the patient was independent in ADLs and ambulation. By 9 months post discharge follow-up, the patient was fully independent with normal cognition, and had self tapered all medications without ill effect. Dopamine agonist trials of appropriate duration appear indicated in cases of movement disorder (paucity or excess) following midbrain lesions.