ACR Appropriateness Criteria Dementia and Movement Disorders.

Neurodegenerative disease, including dementia, extrapyramidal degeneration, and motor system degeneration, is a growing public health concern and is quickly becoming one of the top health care priorities of developed nations. The primary function of anatomic neuroimaging studies in evaluating patients with dementia or movement disorders is to rule out structural causes that may be reversible. Lack of sensitivity and specificity of many neuroimaging techniques applied to a variety of neurodegenerative disorders has limited the role of neuroimaging in differentiating types of neurodegenerative disorders encountered in everyday practice. Nevertheless, neuroimaging is a valuable research tool and has provided insight into the structure and function of the brain in patients with neurodegenerative disorders. Advanced imaging techniques, such as functional neuroimaging with MRI and MR spectroscopy, hold exciting investigative potential for better understanding of neurodegenerative disorders, but they are not considered routine clinical practice at this time. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

ACR Appropriateness Criteria Headache.

Most patients presenting with uncomplicated, nontraumatic, primary headache do not require imaging. When history, physical, or neurologic examination elicits "red flags" or critical features of the headache, then further investigation with imaging may be warranted to exclude a secondary cause. Imaging procedures may be diagnostically useful for patients with headaches that are: associated with trauma; new, worse, or abrupt onset; thunderclap; radiating to the neck; due to trigeminal autonomic cephalgia; persistent and positional; and temporal in older individuals. Pregnant patients, immunocompromised individuals, cancer patients, and patients with papilledema or systemic illnesses, including hypercoagulable disorders may benefit from imaging. Unlike most headaches, those associated with cough, exertion, or sexual activity usually require neuroimaging with MRI of the brain with and without contrast to exclude potentially underlying pathology before a primary headache syndrome is diagnosed. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

ACR appropriateness criteria sinonasal disease.

Sinonasal imaging is performed in 2 major clinical scenarios: inflammatory rhinosinusitis or suspected mass lesion. Rhinosinusitis affects more than 16% of the US population annually. It poses an immense economic burden, accounting for more than 26 million outpatient visits annually and costing more than $4.3 billion annually in direct medical expenses. Most cases of uncomplicated acute and subacute rhinosinusitis are diagnosed clinically and should not require any imaging procedure. CT of the sinuses without contrast is the imaging method of choice in patients with recurrent acute sinusitis or chronic sinusitis. Sinusitis cannot be diagnosed on the basis of imaging findings alone. CT scan findings should be interpreted in conjunction with clinical and endoscopic findings. MRI is currently used for evaluation of sinus disease as a complementary study in cases of aggressive sinus infection with ocular/intracranial complications, potential invasive fungal sinusitis in immunocompromised patients or in the evaluation of a sinonasal mass. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

ACR Appropriateness Criteria(®) myelopathy.

Myelopathy is a problem that requires imaging to distinguish among numerous specifically treatable causes. The first priority is to determine mechanical stability after trauma. Next, it is crucial to distinguish intrinsic disease from extrinsic compression-for example, by epidural abscess. Osteophytes or disc extrusions and metastatic compression are the most common causes of extrinsic lesions. Imaging approaches rely on clinical features such as pain, fever, trauma, and pattern of progression. CT is preferred initially in acute trauma and MRI in all other circumstances. Contrast-enhanced MRI is added when tumor or infection is suspected or with slow or stepwise progression, especially when pain is not prominent. Vascular imaging is used when arteriovenous malformation, fistula, or occlusive disease is suspected. Because the treatment of myelopathy is often complex, treatment planning may require more than one imaging study or sequential examination to assess interval change. The ACR Appropriateness Criteria(®) are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

ACR Appropriateness Criteria® on cerebrovascular disease.

Stroke is the sudden onset of focal neurologic symptoms due to ischemia or hemorrhage in the brain. Current FDA-approved clinical treatment of acute ischemic stroke involves the use of the intravenous thrombolytic agent recombinant tissue plasminogen activator given <3 hours after symptom onset, following the exclusion of intracerebral hemorrhage by a noncontrast CT scan. Advanced MRI, CT, and other techniques may confirm the stroke diagnosis and subtype, demonstrate lesion location, identify vascular occlusion, and guide other management decisions but, within the first 3 hours after ictus, should not delay or be used to withhold recombinant tissue plasminogen activator therapy after the exclusion of acute hemorrhage on noncontrast CT scans. MR diffusion-weighted imaging is highly sensitive and specific for acute cerebral ischemia and, when combined with perfusion-weighted imaging, may be used to identify potentially salvageable ischemic tissue, especially in the period >3 hours after symptom onset. Advanced CT perfusion methods improve sensitivity to acute ischemia and are increasingly used with CT angiography to evaluate acute stroke as a supplement to noncontrast CT. The ACR Appropriateness Criteria(®) are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Differential contextual responses of normal human breast epithelium to ionizing radiation in a mouse xenograft model.

Radiotherapy is a key treatment option for breast cancer, yet the molecular responses of normal human breast epithelial cells to ionizing radiation are unclear. A murine subcutaneous xenograft model was developed in which nonneoplastic human breast tissue was maintained with the preservation of normal tissue architecture, allowing us to study for the first time the radiation response of normal human breast tissue in situ. Ionizing radiation induced dose-dependent p53 stabilization and p53 phosphorylation, together with the induction of p21(CDKN1A) and apoptosis of normal breast epithelium. Although p53 was stabilized in both luminal and basal cells, induction of Ser392-phosphorylated p53 and p21 was higher in basal cells and varied along the length of the ductal system. Basal breast epithelial cells expressed ΔNp63, which was unchanged on irradiation. Although stromal responses themselves were minimal, the response of normal breast epithelium to ionizing radiation differed according to the stromal setting. We also demonstrated a dose-dependent induction of γ-H2AX foci in epithelial cells that was similarly dependent on the stromal environment and differed between basal and luminal epithelial cells. The intrinsic differences between human mammary cell types in response to in vivo irradiation are consistent with clinical observation that therapeutic ionizing radiation is associated with the development of basal-type breast carcinomas. Furthermore, there may be clinically important stromal-epithelial interactions that influence DNA damage responses in the normal breast. These findings demonstrate highly complex responses of normal human breast epithelium following ionizing radiation exposure and emphasize the importance of studying whole-tissue effects rather than single-cell systems.

Management of in situ lobular neoplasia detected on needle core biopsy of breast.

AIMS: To evaluate the risk of having occult ductal carcinoma in situ or invasive carcinoma in the region of a focus of lobular (in situ) neoplasia (LN) diagnosed on needle core biopsy (NCB) of breast. METHODS: All cases of LN diagnosed on NCB of breast over 10 years (2000-2009 inclusive) were reviewed. The clinical presentation, radiological appearances and final pathological diagnosis on open diagnostic biopsy (ODB) were correlated. RESULTS: 125 cases of LN on NCB were identified from diagnostic codes. Of these, 72 (58%) had a coexistent, higher-grade lesion that mandated surgery. Fifty of the remaining 53 (94%) underwent ODB. The majority of patients were asymptomatic, with 68% presenting through the breast screening programme, and in 89% of patients, the target abnormality was microcalcification. Of the 50 patients, 13 (26%) had a final diagnosis of in situ or invasive carcinoma requiring therapeutic surgery. When the cases of pleomorphic LN were excluded, 21% (10/47) were upgraded. Two of these 10 cases had discordant radiology which could have been diagnosed on repeat NCB leaving an upgrade rate of 18% (8/45). In four of the eight cases of invasive malignancy, the disease was multifocal. CONCLUSIONS: LN is frequently asymptomatic, being identified by mammographic microcalcification alone. In 21% of classical LN cases, it is associated with an undiagnosed, higher-grade lesion requiring oncological management. In our view, patients with LN discovered on NCB should undergo open diagnostic biopsy.

Bodyweights and growth rates of spring- and autumn-born Thoroughbred horses raised on pasture.

AIM: To examine the growth of spring- and autumn-born Thoroughbred foals raised on pasture. METHODS: Bodyweight and growth rates were measured in pasture-raised Thoroughbred horses, born in either spring (n=56) or autumn (n=7), from birth to approximately 13 and 17 months of age. RESULTS: Birthweight tended to be lower in autumn- than spring-born foals (54.4, SD 7.92 kg vs 57.3, SD 5.90 kg; p=0.08). Between birth and 6 months of age, there was no difference in growth rate at equivalent ages between horses born in spring and autumn. Spring-born horses, which were weaned in the autumn, had lower post-weaning growth rates than autumn-born horses that were weaned in the spring. At time of the late yearling sales (March-April) in the Southern Hemisphere, unadjusted mean bodyweights of autumn-born horses (379.3, SD 24.8 kg) were lower (p=0.017) than those of the spring-born horses (437.2, SD 35.3 kg), although values in the autumn-born horses were all within two standard deviations (SD) of the mean of the spring-born animals. When adjusted for the covariates of birthweight and gender, the difference between spring- and autumn-born horses at that time was not significant (p=0.25). CONCLUSIONS AND CLINICAL RELEVANCE: Some autumn-born foals could be marketed for late yearling sales in the Southern Hemisphere, on the basis of bodyweight. Furthermore, they might also be competitive in the Northern Hemisphere industry (sales or racing), as they would be competing against horses of the same official age.

A mathematical model for the effect of a false-negative sentinel node biopsy on breast cancer mortality: a tool for everyday use.

One of the concerns of using sentinel node biopsy (SNB) is the risks of a false-negative result (FNR). We have created a mathematical model to estimate the effects of FNR on mortality because of excess local recurrence and adjuvant therapy inappropriately withheld. With a FNR of 9.7%, the absolute effect on 10-year mortality is estimated to be less than 0.6% for all patients with tumours <2 cm in size. Since the impact of FNR on mortality is small and FNR rates do not improve with training, we suggest that detection rate alone is an adequate criterion for judging competence in SNB.

The pituitary and testicular responses to GnRH challenge between 4 and 14 months of age in thoroughbred colts born in spring and autumn.

Gonadotropin releasing-hormone analogue (buserelin) challenges were carried out every 8 weeks from 4 to 14 months of age on thoroughbred colts born in the spring (n = 6) or autumn (n = 5) to define the onset of puberty. In all colts, luteinizing hormone (LH) secretion followed a seasonal pattern, with high baseline and maximal concentrations in the spring and summer and low concentrations in the winter. Testosterone concentrations were undetectable before spring and, thus, autumn-born colts were younger than spring-born colts when a testosterone response to buserelin was first observed. Mean weights of the autumn-born colts were 300 kg (282-327 kg) at the time of the first detectable testosterone response in the following spring (October). Spring-born colts had reached this weight in the winter (May and June, before day length had increased) but did not exhibit a significant testosterone response until the spring at a mean weight of 352 kg (327-403 kg). It is proposed that colts must achieve a threshold body weight concurrently with stimulatory photoperiod for onset of puberty to occur.

Onset of puberty in pasture-raised Thoroughbreds born in southern hemisphere spring and autumn.

REASONS FOR PERFORMING STUDY: There is little information on age, weight and time of year of puberty in Thoroughbred horses, and the interpretation of such data is difficult due to the wide variety of descriptions of the onset of puberty. OBJECTIVES: To examine the age, bodyweight and date of onset of puberty in Thoroughbreds born in spring and autumn. METHODS: Bodyweight data and blood samples were collected in 59 pasture-raised Thoroughbred horses. Five autumn-born and 18 spring-born colts and 3 autumn-born and 33 spring-born fillies were examined from birth to age 13 and 17 months. A testosterone concentration >2 s.d. above the baseline concentration was indicative of onset of puberty in colts; and progesterone concentration >2 ng/ml and at least 3 times greater than the previous progesterone concentration was indicative of a first ovulation in fillies. RESULTS: Spring-born fillies and colts were older and heavier than autumn-born fillies and colts at puberty. The age at onset of puberty in spring- and autumn-born foals was 291-408 days and 212-270 days, respectively. The weight at puberty in spring-born foals was 302-409 kg, and in autumn-born foals was 277-344 kg. However, the mean date at onset of puberty was not significantly different between spring- and autumn-born horses, with puberty occurring in October (New Zealand spring). CONCLUSIONS AND POTENTIAL RELEVANCE: Seasonal changes in photoperiod affect the timing of onset of puberty, provided a minimum threshold bodyweight has been reached. Spring-born horses reached this threshold weight during the winter months and remained reproductively inactive until after the stimulus of increasing day-length occurred. The autumn-born horses reached the threshold weight to support puberty at the same time as stimulatory photoperiod and, therefore, reached puberty significantly younger and lighter than the spring-born horses.

LH and testosterone responses to five doses of a GnRH analogue (buserelin acetate) in 12-month-old Thoroughbred colts.

To determine the responsiveness of the pituitary-gonadal axis of peri-pubertal colts to GnRH, buserelin (0.5, 1, 5, 10 and 40 microg) was given to 13 male Thoroughbred yearlings ( n=3-8 colts per dose). Jugular venous blood samples were taken at -10, 0, 10, 20, 30, 40, 60, 120 and 180 min relative to buserelin administration. Increases (P < 0.05) in LH concentrations occurred in colts that received 5, 10, or 40 microg buserelin, but not in those that received 0.5 or 1 microg. Peak LH concentrations and mean area under the curve were higher (P < 0.05) in colts receiving 40 microg buserelin than in those that received 0.5 or 1 microg. Increases ( P< 0.05) in testosterone concentrations occurred in some, but not all, colts that received 1, 5, 10, or 40 microg buserelin. Neither peak concentration nor area under the curve of testosterone differed significantly among doses of buserelin. The percentage of horses that responded to the buserelin increased with increasing dose, with only the highest dose eliciting LH and testosterone responses in all colts. In conclusion, peri-pubertal colts exhibited a dose-response release of LH following buserelin treatment, but individual colts responded in an "all or nothing" manner, such that each either had an LH response or did not. Some colts that exhibited a significant LH response had no subsequent increase in plasma testosterone concentrations; perhaps the pituitary LH response may not have been great enough to stimulate the Leydig cells in these individuals.

Prediction of foaling using mammary secretion constituents.

AIMS: To test published models for predicting time of foaling using data derived from prepartum mammary secretions and to develop a new model based on concentrations of mammary secretion constituents that accurately predicts time of foaling in Thoroughbred mares. METHODS: Concentrations of sodium, potassium, calcium, citrate and lactose were measured in prepartum mammary secretions of 20 Thoroughbred mares in the 2 weeks before expected date of foaling. Models to predict time of foaling were fitted to data based on absolute concentration, change in concentration, and percentage change in concentration of mammary secretion constituents in relation to actual intervals to foaling. RESULTS: Concentrations of potassium, calcium, citrate and lactose increased, and concentration of sodium decreased as foaling approached but variation between mares was large. Models to predict time of foaling based on percentage change in electrolyte concentrations were less accurate than those based on absolute concentration and change in concentration. When data from this study were fitted to two previously published models, the statistical sensitivity, specificity, and positive and negative predictive values of both models were lower than those originally reported. CONCLUSIONS: The use of prepartum equine mammary secretion electrolyte concentrations for prediction of time of foaling is unreliable, due to large variation in both absolute concentrations and change in concentrations between mares. Models that use a combination of mammary secretion electrolytes and physical and behavioural factors may better predict foaling than those based on mammary secretions alone.