Short communication: Risk factors for sonographically detectable udder edema in overbagged cows at dairy shows.

At dairy cow shows, the appearance of the udder is very important. To show cows at their best, udders are often presented in an overbagged state by extending milking intervals before the show. This practice represents an animal welfare issue because it is associated with behavior changes (e.g., excessive abduction and decreased eating time) and may affect the health of the animal. The aim of the current study was to determine the association between various parameters (e.g., milk yield, days in milk, milking procedures, or administration of nonsteroidal anti-inflammatory drugs, steroids, or diuretics) and the sonographically detectable udder edema score. Data were collected from the show catalogs, by interviewing the exhibitors, by analyzing official veterinary treatment protocols and official milking data, via laboratory analysis of blood samples, and by sonographic examinations of the udders at the show. For sonographically detectable udder edema scoring, 3 scans were taken, 1 on each fore quarter and 1 incorporating both rear quarters at the level of the median suspensory ligament. For grading the scans, a scoring system of 4 grades (score 0 = no edema, 1 = slight edema, 2 = moderate edema, 3 = severe edema) was used. Data from 321 cows of different breeds were collected at 4 highly competitive Swiss dairy shows (shows A-D) between January and September 2017. To determine risk factors for sonographically detectable udder edema, data were analyzed with 2 different logistic regression models. In model 1, the odds ratios were 3.33 (milking intervals of ≥16 h vs. <14 h), 3.84 (show A vs. show C), and 7.39 (dairy breeds vs. dual-purpose breeds). Milking intervals of dairy breeds were significantly higher than those of dual-purpose breeds. In model 2, milking interval was the only significant risk factor with an odds ratio of 9.00 for milking intervals of ≥16 h. Only the milking intervals represented a relevant risk factor in both models; therefore, we concluded that the previously described sonographic udder edema scoring is a useful technique for detecting overbagged udders at dairy shows. Its routine implementation may improve cow welfare at dairy shows.

Technical Note: Real-time image-guided adaptive radiotherapy of a rigid target for a prototype fixed beam radiotherapy system.

PURPOSE: Fixed beam radiotherapy systems utilize couch movement and rotation instead of gantry rotation in order to simplify linear accelerator design. We investigate the ability to deliver fixed beam treatments with the same level of clinical accuracy as conventional (rotating beam) treatments using real-time image guidance to maintain this accuracy in the presence of rigid target motion. METHODS: A prototype fixed beam radiotherapy system was built using a standard linac with the beam fixed in the vertical position and a computer controlled rotation stage that rotated a rigid phantom about the superior-inferior axis. Kilovoltage Intrafraction Monitoring (KIM) and real-time beam adaptation with MLC tracking was applied to a five-field IMRT treatment plan with motion introduced to the phantom. The same IMRT treatment was also delivered with real-time adaptation using the conventional rotating beam geometry. Film dosimetry was used to measure the dose delivered with a fixed beam compared to a rotating beam, as well as to compare treatments delivered with and without real-time adaptation. RESULTS: The dose distributions were found to be equivalent between the fixed beam and rotating beam geometry for real-time adaptive radiotherapy using KIM and MLC tracking beam adaptation. Gamma analysis on the films showed agreement >98% using a 2%/2 mm criteria with adaptation for static shifts and periodic motion. CONCLUSIONS: Fixed beam treatments with real-time beam adaptation are dosimetrically equivalent to conventional treatments with a rotating beam, even in the presence of rigid target motion. This suggests that, for a rigid target, the high clinical accuracy of real-time adaptive radiotherapy can be achieved with simpler beam geometry.

An interdimensional correlation framework for real-time estimation of six degree of freedom target motion using a single x-ray imager during radiotherapy.

Increasing evidence suggests that intrafraction tumour motion monitoring needs to include both 3D translations and 3D rotations. Presently, methods to estimate the rotation motion require the 3D translation of the target to be known first. However, ideally, translation and rotation should be estimated concurrently. We present the first method to directly estimate six-degree-of-freedom (6DoF) motion from the target's projection on a single rotating x-ray imager in real-time. This novel method is based on the linear correlations between the superior-inferior translations and the motion in the other five degrees-of-freedom. The accuracy of the method was evaluated in silico with 81 liver tumour motion traces from 19 patients with three implanted markers. The ground-truth motion was estimated using the current gold standard method where each marker's 3D position was first estimated using a Gaussian probability method, and the 6DoF motion was then estimated from the 3D positions using an iterative method. The 3D position of each marker was projected onto a gantry-mounted imager with an imaging rate of 11 Hz. After an initial 110° gantry rotation (200 images), a correlation model between the superior-inferior translations and the five other DoFs was built using a least square method. The correlation model was then updated after each subsequent frame to estimate 6DoF motion in real-time. The proposed algorithm had an accuracy (±precision) of -0.03 ± 0.32 mm, -0.01 ± 0.13 mm and 0.03 ± 0.52 mm for translations in the left-right (LR), superior-inferior (SI) and anterior-posterior (AP) directions respectively; and, 0.07 ± 1.18°, 0.07 ± 1.00° and 0.06 ± 1.32° for rotations around the LR, SI and AP axes respectively on the dataset. The first method to directly estimate real-time 6DoF target motion from segmented marker positions on a 2D imager was devised. The algorithm was evaluated using 81 motion traces from 19 liver patients and was found to have sub-mm and sub-degree accuracy.

Quantifying the accuracy and precision of a novel real-time 6 degree-of-freedom kilovoltage intrafraction monitoring (KIM) target tracking system.

Target rotation can considerably impact the delivered radiotherapy dose depending on the tumour shape. More accurate tumour pose during radiotherapy treatment can be acquired through tracking in 6 degrees-of-freedom (6 DoF) rather than in translation only. A novel real-time 6 DoF kilovoltage intrafraction monitoring (KIM) target tracking system has recently been developed. In this study, we experimentally evaluated the accuracy and precision of the 6 DoF KIM implementation. Real-time 6 DoF KIM motion measurements were compared against the ground truth motion retrospectively derived from kV/MV triangulation for a range of lung and prostate tumour motion trajectories as well as for various static poses using a phantom. The accuracy and precision of 6 DoF KIM were calculated as the mean and standard deviation of the differences between KIM and kV/MV triangulation for each DoF, respectively. We found that KIM is able to provide 6 DoF motion with sub-degree and sub-millimetre accuracy and precision for a range of realistic tumour motion.

ESTIMATES OF RADIATION DOSES TO THE SKIN FOR PEOPLE CAMPED AT WALLATINNA DURING THE UK TOTEM 1 ATOMIC WEAPONS TEST.

A group of Aboriginal people was camped at Wallatinna in South Australia, ~170 km downwind from Emu Field, where an atomic test (the Totem 1 test) was carried out at 07.00 on 15 October 1953 local time (21.30 on 14 October 1953 GMT (Greenwich Mean Time)). They left the camp ~24 hours later. These people stated that a phenomenon that has become known as a 'black mist' rolled through their camp site ~5 hours after detonation and that some of them subsequently became sick, displaying skin reddening and nausea. They feared that the sickness was a result of exposure to high levels of radiation. The purpose of this paper is to determine if these people could have received ionising radiation doses high enough to cause the symptoms displayed. The methodology used for the dose estimates is described in the paper. The exposure modes considered were external exposure due to the passage of a contaminated plume over the camp site, inhalation of material from this plume, external exposure from material deposited on the ground as the plume passed, and consumption of contaminated food and water. The contaminants considered in the airborne cloud and the ground plume were fission products and unburnt plutonium from the nuclear detonation, and neutron activation products caused by vaporisation of the tower used to position the weapon. The source was approximated by a line source. An upper estimate of the effective doses received is ~4 mSv, which is well below the level at which acute radiation effects are observed. This estimate is consistent with earlier assessments, which did not consider inhalation of the contribution from neutron activation products.

Diagnosis and ultrasonographic appearance of hepatic metastasis in six cases of canine appendicular osteosarcoma (2005-2013).

OBJECTIVES: The aims of this retrospective study were to identify clinical cases of dogs with appendicular osteosarcoma (OSA) in which hepatic metastasis was confirmed, to highlight the use of cytology for its diagnosis and to describe the radiographic and ultrasonographic appearances of the lesion. METHODS: Medical records were retrospectively reviewed for dogs with appendicular OSA and hepatic metastases between January 2005 and January 2013. Reviews of radiographs, ultrasounds and cytology were performed. RESULTS: Six dogs with appendicular OSA and hepatic metastases were identified. The ultrasonographic appearance of metastatic lesions varied, including hyperechoic with shadowing, hyperechoic without shadowing, hypoechoic and mixed echogenicity. In two cases, the hepatic metastases were also evident on thoracic radiographs. The mean survival time from diagnosis of appendicular OSA was 188 days (range 69-363 days) and from diagnosis of hepatic metastases was 35 days (range 2-69 days). Death was tumour-related in all cases. CONCLUSIONS: Hepatic metastasis varies widely in its ultrasonographic appearance. In three of six cases, hepatic metastasis was identified without concurrent pulmonary metastasis; therefore, abdominal ultrasound may be useful at regular intervals for patient evaluation, especially in clinical trials where accurate identification of the disease-free interval is crucial. Once hepatic metastasis is confirmed, survival times appear limited.

Determining appropriate imaging parameters for kilovoltage intrafraction monitoring: an experimental phantom study.

Kilovoltage intrafraction monitoring (KIM) utilises the kV imager during treatment for real-time tracking of prostate fiducial markers. However, its effectiveness relies on sufficient image quality for the fiducial tracking task. To guide the performance characterisation of KIM under different clinically relevant conditions, the effect of different kV parameters and patient size on image quality, and quantification of MV scatter from the patient to the kV detector panel were investigated in this study. Image quality was determined for a range of kV acquisition frame rates, kV exposure, MV dose rates and patient sizes. Two methods were used to determine image quality; the ratio of kV signal through the patient to the MV scatter from the patient incident on the kilovoltage detector, and the signal-to-noise ratio (SNR). The effect of patient size and frame rate on MV scatter was evaluated in a homogeneous CIRS pelvis phantom and marker segmentation was determined utilising the Rando phantom with embedded markers. MV scatter incident on the detector was shown to be dependent on patient thickness and frame rate. The segmentation code was shown to be successful for all frame rates above 3 Hz for the Rando phantom corresponding to a kV to MV ratio of 0.16 and an SNR of 1.67. For a maximum patient dimension less than 36.4 cm the conservative kV parameters of 5 Hz at 1 mAs can be used to reduce dose while retaining image quality, where the current baseline kV parameters of 10 Hz at 1 mAs is shown to be adequate for marker segmentation up to a patient dimension of 40 cm. In conclusion, the MV scatter component of image quality noise for KIM has been quantified. For most prostate patients, use of KIM with 10 Hz imaging at 1 mAs is adequate however image quality can be maintained and imaging dose reduced by altering existing acquisition parameters.

Quality assurance for the clinical implementation of kilovoltage intrafraction monitoring for prostate cancer VMAT.

PURPOSE: Kilovoltage intrafraction monitoring (KIM) is a real-time 3D tumor monitoring system for cancer radiotherapy. KIM uses the commonly available gantry-mounted x-ray imager as input, making this method potentially more widely available than dedicated real-time 3D tumor monitoring systems. KIM is being piloted in a clinical trial for prostate cancer patients treated with VMAT (NCT01742403). The purpose of this work was to develop clinical process and quality assurance (QA) practices for the clinical implementation of KIM. METHODS: Informed by and adapting existing guideline documents from other real-time monitoring systems, KIM-specific QA practices were developed. The following five KIM-specific QA tests were included: (1) static localization accuracy, (2) dynamic localization accuracy, (3) treatment interruption accuracy, (4) latency measurement, and (5) clinical conditions accuracy. Tests (1)-(4) were performed using KIM to measure static and representative patient-derived prostate motion trajectories using a 3D programmable motion stage supporting an anthropomorphic phantom with implanted gold markers to represent the clinical treatment scenario. The threshold for system tolerable latency is <1 s. The tolerances for all other tests are that both the mean and standard deviation of the difference between the programmed trajectory and the measured data are <1 mm. The (5) clinical conditions accuracy test compared the KIM measured positions with those measured by kV/megavoltage (MV) triangulation from five treatment fractions acquired in a previous pilot study. RESULTS: For the (1) static localization, (2) dynamic localization, and (3) treatment interruption accuracy tests, the mean and standard deviation of the difference are <1.0 mm. (4) The measured latency is 350 ms. (5) For the tests with previously acquired patient data, the mean and standard deviation of the difference between KIM and kV/MV triangulation are <1.0 mm. CONCLUSIONS: Clinical process and QA practices for the safe clinical implementation of KIM, a novel real-time monitoring system using commonly available equipment, have been developed and implemented for prostate cancer VMAT.

DMLC tracking and gating can improve dose coverage for prostate VMAT.

PURPOSE: To assess and compare the dosimetric impact of dynamic multileaf collimator (DMLC) tracking and gating as motion correction strategies to account for intrafraction motion during conventionally fractionated prostate radiotherapy. METHODS: A dose reconstruction method was used to retrospectively assess the dose distributions delivered without motion correction during volumetric modulated arc therapy fractions for 20 fractions of five prostate cancer patients who received conventionally fractionated radiotherapy. These delivered dose distributions were compared with the dose distributions which would have been delivered had DMLC tracking or gating motion correction strategies been implemented. The delivered dose distributions were constructed by incorporating the observed prostate motion with the patient's original treatment plan to simulate the treatment delivery. The DMLC tracking dose distributions were constructed using the same dose reconstruction method with the addition of MLC positions from Linac log files obtained during DMLC tracking simulations with the observed prostate motions input to the DMLC tracking software. The gating dose distributions were constructed by altering the prostate motion to simulate the application of a gating threshold of 3 mm for 5 s. RESULTS: The delivered dose distributions showed that dosimetric effects of intrafraction prostate motion could be substantial for some fractions, with an estimated dose decrease of more than 19% and 34% from the planned CTVD99% and PTV D95% values, respectively, for one fraction. Evaluation of dose distributions for DMLC tracking and gating deliveries showed that both interventions were effective in improving the CTV D99% for all of the selected fractions to within 4% of planned value for all fractions. For the delivered dose distributions the difference in rectum V65% for the individual fractions from planned ranged from -44% to 101% and for the bladder V65% the range was -61% to 26% from planned. The application of tracking decreased the maximum rectum and bladder V65% difference to 6% and 4%, respectively. CONCLUSIONS: For the first time, the dosimetric impact of DMLC tracking and gating to account for intrafraction motion during prostate radiotherapy has been assessed and compared with no motion correction. Without motion correction intrafraction prostate motion can result in a significant decrease in target dose coverage for a small number of individual fractions. This is unlikely to effect the overall treatment for most patients undergoing conventionally fractionated treatments. Both DMLC tracking and gating demonstrate dose distributions for all assessed fractions that are robust to intrafraction motion.

Liver transplantation for the treatment of homozygous familial hypercholesterolaemia in an era of emerging lipid-lowering therapies.

Homozygous familial hypercholesterolaemia (FH) causes severe premature coronary artery disease because of very high levels of low density lipoprotein (LDL)-cholesterol. Standard lipid-lowering drugs and LDL-apheresis may not be sufficiently effective. Liver transplantation replaces defective LDL receptors and vastly improves the lipid profile, and we present the first report of an Australian adult to receive this treatment. Emerging drug treatments for FH may be alternatives to LDL-apheresis and transplantation, but long-term safety and efficacy data are lacking for all of these options.

Association between absolute tumor burden and serum bone-specific alkaline phosphatase in canine appendicular osteosarcoma.

BACKGROUND: In dogs with appendicular osteosarcoma (OSA), increased pretreatment serum bone-specific alkaline phosphatase (BALP) activity is a negative prognostic factor, associated with shorter disease-free intervals and survival times, but a biologic basis for observed differential serum BALP activities in canine OSA patients remains incompletely defined. OBJECTIVE: Serum BALP activity will correlate with absolute tumor burden in dogs with OSA. ANIMALS: This study included 96 client-owned dogs with appendicular OSA. METHODS: In canine OSA cell lines, the expression and membranous release of BALP was evaluated in vitro. The correlation between serum BALP activity and radiographic primary tumor size was evaluated in OSA-bearing dogs. In dogs developing visceral OSA metastases, serial changes in serum BALP activities were evaluated in relation to progression of macroscopic metastases, and visceral metastatic OSA cells were evaluated for BALP expression. RESULTS: In vitro, BALP expression was not associated with either tumorigenic or metastatic phenotype, rather the quantity of membranous BALP released was proportional with cell density. In dogs devoid of macroscopic metastases, there was a positive correlation between serum BALP activity and absolute primary tumor size. In dogs with progressive OSA metastases, serum BALP activity increased and coincided with the development of macroscopic metastases. OSA cells derived from visceral metastatic lesions retained BALP expression. CONCLUSIONS AND CLINICAL IMPORTANCE: Tumor burden is a determinant of serum BALP activity in dogs with appendicular OSA. The association between increased pretreatment BALP activity and negative clinical prognosis may simply be attributed to greater initial tumor burden, and consequently more advanced tumor stage.

FBXW7 regulates glucocorticoid response in T-cell acute lymphoblastic leukaemia by targeting the glucocorticoid receptor for degradation.

Loss of function mutation in FBXW7, an E3 ubiquitin ligase, is associated with good prognosis and early glucocorticoid treatment response in childhood T-cell acute lymphoblastic leukemia (T-ALL) by unknown mechanisms. Here, we show that FBXW7 targets the glucocorticoid receptor α (GRα) for ubiquitylation and proteasomal degradation in a manner dependent on glycogen synthase kinase 3 ß-mediated phsophorylation. FBXW7 inactivation caused elevated GRα levels, and enhanced the transcriptional response to glucocorticoids. There was significant enhancement of GR transcriptional responses in FBXW7-deficient cell lines and primary T-ALL samples, in particular, for those pro-apoptotic regulatory proteins, BIM and PUMA. Reduced FBXW7 expression or function promoted glucocorticoid sensitivity, but not sensitivity to other chemotherapeutic agents used in T-ALL. Moreover, this was a general feature of different cancer cell types. Taken together, our work defines GRα as a novel FBXW7 substrate and demonstrates that favorable patient prognosis in T-ALL is associated with FBXW7 mutations due to enhanced GRα levels and steroid sensitivity. These findings suggest that inactivation of FBXW7, a putative tumor suppressor protein, may create a synthetic lethal state in the presence of specific anticancer therapies.

Immunoregulatory cytokines are associated with protection from immunopathology following Mycobacterium avium subspecies paratuberculosis infection in red deer.

Although the causative agent of Johne's disease, Mycobacterium avium subsp. paratuberculosis, is well known, the etiology of disease and the immune responses generated in response to infection are still poorly understood. Knowledge of definitive markers of protective immunity, infection, and the establishment of chronic granulomatous Johne's disease is necessary to advance vaccine and diagnostic development. We sought to profile the immune responses occurring within jejunal lymph nodes of experimentally challenged red deer (Cervus elaphus). Quantitative PCR was utilized to measure a range of cytokines, signaling molecules, and transcription factors involved in Th1, Th2, Treg, and Th17 immune responses. Significant differences in gene expression were observed between control, minimally diseased, and severely diseased animals, with severely diseased animals showing elevated proinflammatory transcripts and reduced anti-inflammatory transcripts. We identified a proinflammatory cytokine milieu of gamma interferon, interleukin-1α (IL-1α), and IL-17, which may contribute to the immunopathology observed during clinical Johne's disease and suggest that Th2 and Treg immune responses may play an important role in controlling the development of immunopathology in infected animals.

'The average Scottish man has a cigarette hanging out of his mouth, lying there with a portion of chips': prospects for change in Scottish men's constructions of masculinity and their health-related beliefs and behaviours.

Men's apparent resistance to recommended health practices and their engagement with 'high-risk' behaviours has been associated with an increased risk of morbidity or mortality. Recent work has highlighted the need to think critically about the health-promoting behaviours that men appear reluctant to engage in, as well as examining those they embrace, and explore the gendered meanings that men attribute to their beliefs and behaviours. This article presents men's discussions of the 'practices of masculinity' and examines their relation to, and implications for, men's health-related behaviours as articulated in 15 focus group discussions (59 participants in total). The data capture both the experiences of men who felt pressured to engage in behaviours that may be harmful to their health in order to appear masculine and the accounts of those who regarded themselves as freer to embrace salutogenic health practices. Less is known about the circumstances that might encourage men to re-think their engagement in performances of masculinity that have potentially detrimental effects on their health. The data presented here suggest that ageing, illness, and fatherhood were some of the experiences that prompted men to re-evaluate their health practices.

Contrast harmonic ultrasound of spontaneous liver nodules in 32 dogs.

Thirty-two dogs with spontaneous hepatic nodules were given intravenous ultrasound contrast medium (Definity or Sonovue) and imaged with contrast harmonic software on a conventional ultrasound machine system. Digital video images were initially reviewed to describe the perfusion pattern of malignant nodules. The images were reviewed again to test this pattern against all individual nodules. Subjectively, there was improved conspicuity of malignant nodules after contrast enhancement compared with conventional imaging and increased numbers of malignant nodules were often noted. There was decreased conspicuity of benign nodules and no additional nodules were seen after contrast enhancement. There was a highly significant (P < 0.0001) association of malignancy with a hypoechoic nodule at surrounding normal liver peak contrast enhancement. Benign nodules were isoechoic to the surrounding normal liver at peak contrast enhancement. Only one benign nodule (hepatoma) had regions of hypoechogenicity compared with the surrounding normal liver at peak liver contrast enhancement. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were highly significant (P < 0.0001) (100%, 94.1%, 93.8%, 100%, and 96.9%, respectively). No complications or morbidity was noted throughout the course of the study. Contrast harmonic ultrasound appears to be accurate at discriminating between naturally occurring benign and malignant nodules in the liver of dogs.

Evaluation of co-morbidity indices in patients admitted for chronic obstructive pulmonary disease.

BACKGROUND: There is limited and conflicting information on the use of co-morbidity instruments to predict mortality in patients with chronic obstructive pulmonary disease (COPD). METHODS: We sought to test the validity of the Charlson Index and another co-morbidity instrument, the Adult co-morbidity evaluation 27 (ACE-27), in patients admitted with COPD exacerbations. Co-morbidity scores were obtained by chart review. Information on mortality was retrieved from the Social Security Death Index. We examined the predictive validity of the Charlson and the ACE-27 using survival analysis. RESULTS: There were 112 patients eligible for the study. The ACE-27 but not the Charlson predicted survival, after adjusting for age, gender, and smoking history in Cox regression, hazard ratio (95% CI) of 1.99 (1.17-3.39). CONCLUSIONS: This study confirms earlier findings that the Charlson Index is not a reliable predictor of mortality in patients with COPD. However, the ACE-27 appears to be useful for predicting survival in this study.

Extensive and preferential Fas/Fas ligand-dependent death of gammadelta T cells following infection with Listeria monocytogenes.

In the spleens of mice infected intraperitoneally with the bacterium Listeria monocytogenes, both alphabeta and gammadelta T cells became rapidly activated, followed by a massive apoptotic death response predominantly within the gammadelta population. The death response involved two major splenic gammadelta T-cell subsets and was Fas/Fas ligand (Fas-L)-dependent. Among T cells isolated from the Listeria-infected spleen, Fas-L was almost exclusively expressed in gammadelta T cells. gammadelta T cells coexpressed Fas and Fas-L, suggesting activation-induced suicide as a mechanism of their death. In vivo treatment with an antibody specific for CD3epsilon induced activation, preferential Fas-L expression and apoptosis of gammadelta T cells, resembling the response pattern in listeriosis, whereas antibodies specific for T-cell receptor-beta (TCR-beta) or TCR-delta did not, suggesting that the complete response seen in listeriosis requires both gammadelta TCR engagement and additional stimuli. L. monocytogenes causes early nonspecific, Fas-independent lymphocyte death in heavily infected tissues. In contrast, the death response described here is selective, Fas-dependent and triggered at low local levels of bacteria, suggesting that it is controlled by interactions with other infection-activated host cells, and perhaps part of a regulatory circuit specifically curtailing gammadelta T cells.

MAOB intron 13 and COMT codon 158 polymorphisms, cigarette smoking, and the risk of PD.

BACKGROUND: A polymorphism (G to A transition) in intron 13 of the mitochondrial enzyme monoamine oxidase B (MAOB) gene may modify, alone or by interacting with the catechol-O-methyltransferase (COMT(LL)) genotype (low enzymatic activity), the risk of idiopathic PD. Also, the association between never smoking and PD risk may be present only in people with the MAOB G allele. METHODS: The authors studied two ongoing prospective cohorts-the Nurses' Health Study (121,700 women aged 30 to 55 in 1976) and the Health Professionals' Follow-up Study (51,529 men aged 40 to 75 in 1986). They identified new PD cases through 1996, selected random control subjects matched on age and study cohort, and obtained DNA samples from blood or buccal smears from 85% of the eligible cases and 84% of the control subjects. They included genotypes from 214 cases and 449 control subjects, all Caucasian. RESULTS: The odds ratio of PD was 1.2 (95% CI 0.9, 1.7) for MAOB genotypes G/GG/GA compared with genotypes A/AA, and 1.1 (0.7, 1.8) for COMT genotypes LL compared with HH. The odds ratio (95% CI) was 1.7 (0.7, 3.9) for those with MAOB G/GG and COMT(LL) genotypes compared with those with MAOB A/AA and COMT(HH). There was a strong association between never smoking and PD risk in all groups defined by MAOB and COMT genotypes. CONCLUSION: The findings do not support a major role of the MAOB intron 13 polymorphism in the development of PD, either by itself or by interacting with smoking.