Potentiation of M1 Muscarinic Receptor Reverses Plasticity Deficits and Negative and Cognitive Symptoms in a Schizophrenia Mouse Model.

Schizophrenia patients exhibit deficits in signaling of the M1 subtype of muscarinic acetylcholine receptor (mAChR) in the prefrontal cortex (PFC) and also display impaired cortical long-term depression (LTD). We report that selective activation of the M1 mAChR subtype induces LTD in PFC and that this response is completely lost after repeated administration of phencyclidine (PCP), a mouse model of schizophrenia. Furthermore, discovery of a novel, systemically active M1 positive allosteric modulator (PAM), VU0453595, allowed us to evaluate the impact of selective potentiation of M1 on induction of LTD and behavioral deficits in PCP-treated mice. Interestingly, VU0453595 fully restored impaired LTD as well as deficits in cognitive function and social interaction in these mice. These results provide critical new insights into synaptic changes that may contribute to behavioral deficits in this mouse model and support a role for selective M1 PAMs as a novel approach for the treatment of schizophrenia.

High sensitivity magnetometer for measuring the isotropic and anisotropic magnetisation of small samples.

We describe how the full, isotropic and anisotropic, magnetisation of samples as small as tens of micrometers in size can be sensitively measured using a piezoresistive microcantilever and a small, moveable ferromagnet. Depending on the position of the ferromagnet, a strong but highly local field gradient of up to ∼4200 T/m can be applied at the sample or removed completely during a single measurement. In this way, the magnetic force and torque on the sample can be independently determined without moving the sample or cycling the experimental system. The technique can be used from millikelvin temperatures to ∼85 K and in magnetic fields from 2 T to the highest fields available. We demonstrate its application in measurements of the semimagnetic semiconductor Hg(1 - x)Fe(x)Se, where we achieved a moment sensitivity of better than 2.5 × 10(-14) J/T for both isotropic and anisotropic components.

Pregnancy toxemia of ewes, does, and beef cows.

Pregnancy toxemia commonly affects pregnant ewes and does during late gestation. This metabolic disease is thought to result from disruption of the dam's glucose homeostatic mechanism in response to increased nutritional demands of the rapidly developing fetal placental unit. Commercial production systems are comprised of a variety of nutritional, metabolic, genetic, physiologic, environmental, economic, health, and management factors that singularly or as a group influence the clinical expression of pregnancy toxemia. Recognizing the role management plays in controlling these inputs is crucial to pregnancy toxemia prevention and treatment programs.

Use of a non-linear spline regression to model time-varying fluctuations in mammary-secretion element concentrations of periparturient mares in Michigan, USA.

A study was designed to model the fluctuations of nine specific element concentrations in mammary secretions from periparturient mares over time. During the 1992 foaling season, serial samples of mammary secretions were collected from all 18 pregnant Arabian mares at the Michigan State University equine teaching and research center. Non-linear regression techniques were used to model the relationship between element concentration in mammary secretions and days from foaling (which connected two separate sigmoid curves with a spline function); indicator variables were included for mare and mare parity. Element concentrations in mammary secretions varied significantly during the periparturient period in mares. Both time trends and individual variability explained a significant portion of the variation in these element concentrations. Multiparous mares had lower concentrations of K and Zn, but higher concentrations of Na. Substantial serial and spatial correlation were detected in spite of modeling efforts to avoid the problem. As a result, p-values obtained for parameter estimates were likely biased toward zero. Nonetheless, results of this analysis indicate that monitoring changes in mammary-secretion element concentrations might reasonably be used as a predictor of impending parturition in the mare. In addition, these results suggest that element concentrations warrant attention in the development of neonatal milk-replacement therapies. This study demonstrates that non-linear regression can be used successfully to model time-series data in animal-health management. This approach should be considered by investigators facing similar analytical challenges.

Risk factors for colic in the Michigan (USA) equine population.

A population-based prospective epidemiological study was conducted to assess risk factors for equine colic. A stratified sample of 3925 equids in 138 randomly selected equine farms in the state of Michigan was monitored in two 12-month rounds of data collection. Incidence densities were used to describe the rate of development of colic in the study population. Mortality rates, case fatality rates and survival rates were used to describe the severity of colic on the study population. Multivariable logistic regressions with random effects (grouped according to farm) were used to identify risk factors associated with occurrence of colic. A total of 3175 equids from 132 farms from the starting population of 3925 equids in 138 farms was used in the multivariable analysis. There were 77 cases of colic reported during the study period in 62 animals. Of these animals, 54 (87%) had one case, 5 (8%) had two cases, 2 (3%) had three cases, and 1 (2%) had seven cases. Of the cases reported, 49 (64%) were non-specific diagnoses, 13 (17%) impaction/acute intestinal obstruction colics, 7 (9%) spasmodic colics, 4 (5%) sand colics, 2 (3%) gas colics, 1 (1%) verminous mesenteric arteritis, and 1 (1%) enteritis due to ingestion of moldy grain. The annual incidence density of colic in the study was 3.5 cases per 100 equid-years. The surgical treatment risk was 17% (13/77). The overall mortality risk due to colic was 0.5 deaths per 100 equids, and the case fatality risk was 13% (10/77). The case fatality risk for cases treated surgically was 31% (4/13), while the case fatality risk for non-surgical colics was 10% (7/69). Risk factors associated with significantly increased likelihood of developing colic were foaling during the study, deworming during the study, increased age, and participation in showing activities. Geldings and equids provided group drinking water from sources other than tanks, buckets and automatic waterers were significantly associated with reduced risk of colic.

Multi-element assay of mammary secretions and sera from periparturient mares by inductively coupled argon plasma emission spectroscopy.

OBJECTIVE: To document and determine changes in the mineral profiles of sera and mammary secretions from a population of periparturient mares. ANIMALS: 18 clinically normal periparturient Arabian broodmares. PROCEDURE: Inductively coupled argon emission spectroscopy was used to measure Ca, Cu, Fe, K, Mg, Mn, Na, P, and Zn concentrations in sera and mammary secretions of periparturient mares. In addition, S was measured in mammary secretions. RESULTS: Serum concentrations of Ca, Cu, Fe, K, Mg, Na, P, and Zn remained constant throughout late pregnancy and the first 7 days of lactation. Compared with values on day 11 before foaling, mammary fluid concentrations of Ca, Cu, K, Mg, P, S, and Zn increased prior to parturition and all element concentrations, except Ca, decreased with the onset of lactation. In contrast, Na concentrations in mammary secretions decreased precipitously as parturition approached. Iron concentrations in mammary secretions remained relatively constant up to the time of parturition, decreased at parturition, and remained constant during lactation. CONCLUSIONS AND CLINICAL RELEVANCE: Prior to foaling, increasing concentrations of Ca, Cu, K, Mg, P, S, or Zn in mammary secretions in concert with precipitous decreases in Na concentrations may provide a predictive index of impending parturition in the mare and a means of assessing fetal readiness for birth.

Wound care pain management.

Undertreatment of all types of acute and chronic pain is common, both in the United States and around the world. Moreover, a literature review of pressure ulcer pain and its management suggests that this area of pain medicine is truly in its infancy. This article includes a discussion of current literature, anatomy and physiology of pain related to pressure and ischemic ulcers, and assessment methods. It also describes treatment modalities, including conservative measures, medication management, and invasive procedures. Special emphasis is placed on the use of opioid analgesics in the management of severe acute and chronic wound pain.

Wound care pain management.

Undertreatment of all types of acute and chronic pain is common, both in the United States and around the world. Moreover, a literature review of pressure ulcer pain and its management suggests that this area of pain medicine is truly in its infancy. This article includes a discussion of current literature, anatomy and physiology of pain related to pressure and ischemic ulcers and assessment methods. It also describes treatment modalities, including conservative measures, medication management and invasive procedures. Special emphasis is placed on the use of opioid analgesics in the management of severe acute and chronic wound pain.

Pectoralis major muscle rupture in windsurfing.

Board sailing (windsurfing) has become a popular water recreational activity. However, there is little in the medical literature concerning musculoskeletal complications resulting from participation in this sport. We present the first reported case of pectoralis major rupture sustained during board sailing. The patient was initially misdiagnosed, which happens commonly when this muscle ruptures. Only after conservative management failed was the correct diagnosis made and appropriate surgical intervention provided. Proper technique in board sailing requires sustained isometric contraction of the pectoralis major, deltoid and scapular stabilizers to maintain appropriate pull of the sail against wind resistance. Sharp increases in wind speed underly the mechanism of injury. Ruptures of the pectoralis major are usually complete, occur at or near the humeral insertion, and can be associated with misleading physical signs. Therefore, anatomy, clinical findings, surgical technique, and the postoperative rehabilitation program are stressed as to expedite diagnosis and maximize functional outcome.

Complications associated with intermittent pneumatic compression.

The intermittent pneumatic compression device (IPCD) is prophylaxis for prevention of deep-venous thrombosis (DVT). This pneumatic leg sleeve has been used extensively in high-risk surgical patients, without complication. We describe two cases, one with peroneal neuropathy and the other with compartment syndrome, associated with IPCD use during surgery. Case 1 involves a patient with pancreatic cancer and weight loss who developed bilateral peroneal nerve palsies during surgery. Case 2 involves a patient with bladder cancer who developed lower leg compartment syndrome during prolonged surgery in the lithotomy position. These cases are unusual for several reasons. First, patients wearing IPCDs during surgery are at increased risk of neurovascular compression. Second, significant weight loss may predispose the peroneal nerve to injury from intermittent compression garments. Third, patients undergoing surgery in the lithotomy position are at risk of compartment syndrome. Therefore, physicians may wish to use another method of DVT prophylaxis in surgical patients with cancer or significant weight loss, or those who are undergoing procedures in the lithotomy position.

Spinal accessory nerve palsy: an unusual complication of coronary artery bypass.

The neurologic complications of coronary artery bypass surgery have been well documented, with a reported incidence of 61% in one large study. Most injuries to the peripheral nervous system involve the brachial plexus. We report the first case of a spinal accessory nerve lesion after coronary bypass surgery. The patient presented with progressive right shoulder weakness. Electrodiagnostic studies revealed a partial lesion of the right spinal accessory nerve. Physical therapy, including strengthening, range of motion, and electric stimulation to the right shoulder, was prescribed to assist recovery of strength and function. Repeat electrodiagnostic studies confirmed nerve regeneration. Prompt recognition of spinal accessory nerve damage after coronary bypass surgery is essential. Early rehabilitation will improve the chances of a better functional outcome.

Diagnosis and control of neonatal losses in sheep.

Perinatal mortality is affected by a variety of management factors and disease processes that create significant losses for the sheep industry. Annual production losses prior to weaning include roughly 15% to 20% of the lamb crop. The majority of these perinatal losses occur during the prenatal, natal, and early postnatal periods, with the predominant wave of mortality occurring during the first several days following birth. Causes of perinatal mortality may vary between flocks and between geographic areas; however, four dominant categories of lamb loss consistently surface: (1) abortions; (2) hypothermia, starvation, and exposure; (3) pneumonia; and (4) stillbirth and dystocia. They account for roughly 50% to 75% of all documented perinatal losses. Veterinarians and producers need to work together to document the type of losses that occur in a given flock and then design economic prevention programs that address these problems. In most cases, traditional prevention programs will need to be replaced by a comprehensive management scheme addressing nutrition, genetics, housing, marketing, lambing husbandry, and labor.

Lower extremity weakness as the initial manifestation of lung cancer.

A 55-year-old woman had progressive lower extremity weakness. She had an 80-pack-per-year history of cigarette smoking. Electromyographic findings were consistent with the Lambert-Eaton myasthenic syndrome. Despite a normal chest x-ray, normal laboratory studies, and negative bronchoscopy, investigation for lung cancer was pursued. The final thoracotomy and pathology reports indicated a diagnosis of oat cell carcinoma. After treatment with chemotherapy and radiation therapy, clinical and electrophysiologic findings have resolved. Two years after diagnosis, the patient remains in good health without evidence of recurrence.

Thrombosis of axillary-femoral bypass secondary to prosthesis suspension belt.

Patients with peripheral vascular disease and lower extremity amputation frequently undergo arterial bypass surgery to salvage the opposite leg. Compression of axillary-femoral bypass grafts can occur from a variety of causes. The primary physician should monitor graft pulses closely. Compression should be avoided by using forearm crutches instead of axillary crutches. Waist belts for prosthetic support should not be used, and alternatives such as a thigh corset or shoulder suspension should be used. The patient should avoid sleeping on the graft, using a wrist restraint when necessary. If the patient gains weight, garments should be adjusted so as not to be constricting. Upper extremity exercises, particularly in should abduction and extension, should not be so vigorous as to put tension on the graft. A 77-year-old woman with a left below-knee amputation underwent an axillary-femoral bypass for right lower extremity arterial insufficiency which subsequently thrombosed due to compression by the waist belt of her below-knee prosthesis. A series of guidelines are outlined, so that the physiatrist can help maintain graft patency, prolong limb salvage, and avert similar complications in such patients.