Testing spatial working memory in pigs using an automated T-maze.

Pigs are an important large animal model for translational clinical research but underutilized in behavioral neuroscience. This is due, in part, to a lack of rigorous neurocognitive assessments for pigs. Here, we developed a new automated T-maze for pigs that takes advantage of their natural tendency to alternate. The T-maze has obvious cross-species value having served as a foundation for cognitive theories across species. The maze (17' × 13') was constructed typically and automated with flanking corridors, guillotine doors, cameras, and reward dispensers. We ran nine pigs in (1) a simple alternation task and (2) a delayed spatial alternation task. Our assessment focused on the delayed spatial alternation task which forced pigs to wait for random delays (5, 60, 120, and 240 s) and burdened spatial working memory. We also looked at self-paced trial latencies, error types, and coordinate-based video tracking. We found pigs naturally alternated but performance declined steeply across delays (R2 = 0.84). Self-paced delays had no effect on performance suggestive of an active interference model of working memory. Positional and head direction data could differentiate subsequent turns on short but not long delays. Performance levels were stable over weeks in diverse strains and sexes, and thus provide a benchmark for future neurocognitive assessments in pigs.

Medical and gynecological comorbidities in adult women with Turner syndrome: our multidisciplinary clinic experience.

Objective: Women with Turner syndrome (TS) are at increased risk for chronic health conditions. Reports describing the presence of comorbidities in older adult women with TS are limited. This study aimed to examine the prevalence of endocrine, gynecological, and other chronic medical conditions in a cohort of adult TS patients.Methods: A retrospective chart review was conducted on patients seen between 1 February 2015 and 1 July 2018 in a multidisciplinary TS clinic at a university-based ambulatory hospital in Toronto, Canada. All women seen at the TS clinic with a diagnosis of TS aged >18 years were included. The prevalence of diseases was determined overall and stratified by age (<40 and ≥40 years). Statistical comparisons were done using the chi-square test. The main study outcomes included the presence of comorbidities.Results: Of 122 adult women with TS, 24.5% had hypothyroidism, 16% had dysglycemia, and 27.9% had decreased bone mass. Hypothyroidism and dysglycemia were more common among older women (respectively age ≥40 years vs. age <40 years: 36.7% vs. 17.8%, p = 0.018; and 24.5% vs. 5.5%, p = 0.023). Gynecological conditions were identified in 35% of patients and were more common among older women (42.8% age ≥40 years vs. 13.7% age <40 years, p = 0.003). Overall, 41% had hearing impairment, 36.1% had cardiac abnormalities, 14.8% had hypertension, 18.8% had renal abnormalities, and 9% had celiac disease.Conclusions: The results of this study indicate a high prevalence of medical conditions in women with TS, especially those ≥40 years of age. Our study underscores the importance of multidisciplinary adult TS clinics for ongoing screening and management of comorbidities.

Retrospective review of cerebral mycotic aneurysms in 26 patients: focus on treatment in strongly immunocompromised patients with a brief literature review.

BACKGROUND AND PURPOSE: Cerebral mycotic aneurysms are a rare and deadly type of aneurysm that have no definitive treatment guidelines. Our purpose was to retrospectively review known or suspected cases of CMA in order to identify patient populations that may be associated with higher morbidity and mortality. We hope that the identification of patients with these risk factors will lead to early stratification upon presentation, and more urgent treatment of their CMAs. We also hoped to identify any benefit or complication that was specific to either the endovascular or neurosurgical repair of CMAs. MATERIALS AND METHODS: A retrospective multi-institutional study was performed examining cases of CMA during a 15-year period. Patients were considered strongly immunocompromised if there were long-term severely immunocompromised states: AIDS, chemotherapy, or steroid immunosuppression. Patients were excluded if angiographic findings suggested an alternative diagnosis or if an infectious etiology was unknown. Antibiotics were considered "noninvasive treatment." Endovascular and neurosurgical repair were considered "invasive treatment." Data were recorded by reviewing electronic medical records and imaging reports. RESULTS: Twenty-six patients with 40 CMAs were included. Three patients were considered strongly immunocompromised and presented with 4 CMAs, which demonstrated larger average size and more rapid growth; 3 of these patients' aneurysms were treated invasively in the acute period, with the one that was not ruptured causing death. Technical success (aneurysm occlusion without rupture or recanalization) and clinical success (no neurologic complication attributable to the intervention) were obtained equally endovascularly and neurosurgically. Clipping was aborted in favor of coiling for 1 patient. Anticoagulation needed reversal before 2 patients underwent craniotomy for clipping after valve replacement. For CMAs treated with antibiotics alone with angiographic follow-up (n=11), initial aneurysm size was unrelated to persistence and 64% completely regressed. CONCLUSIONS: We recommend initial invasive treatment for CMAs in strongly immunocompromised patients. Testing for underlying immunocompromised states is warranted in patients with CMAs. Endovascular treatment is favored over neurosurgical treatment in patients requiring acute cardiac valve repair due to delays with anticoagulation reversal.

Menstrual suppression for adolescents with developmental disabilities.

The approach to menstrual suppression for adolescents with developmental disabilities has evolved considerably over the years due to changing philosophies and evolving treatment options. We review the medical management options available for menstrual suppression with a focus on the needs and treatment of adolescents with developmental disabilities.

Effort has a greater effect on test scores than severe brain injury in compensation claimants.

Nine-hundred and four consecutive patients, including 80 neurological patients and 470 with head injuries, were given neuropsychological tests. All 43 test scores were converted to normative Z-scores and averaged, giving an Overall Test Battery Mean (OTBM). A variable measuring effort correlated 0.73 with the OTBM. The OTBM mean score was 1.20 SD lower in those who failed the Word Memory Test (WMT) than in those who passed the WMT. Sub-optimal effort suppressed the OTBM 4.5 times more than did moderate-severe brain injury. When only those making a good effort were included, patients with severe brain injuries and neurological diseases scored significantly lower than groups presumed to have no neurological impairment, but these group differences were not seen when all cases were analysed together. These data illustrate the importance of measuring and controlling for sub-optimal effort in individual neuropsychological evaluations, as well as in empirical research with similar groups of patients.

Effort testing in patients with fibromyalgia and disability incentives.

OBJECTIVE: To examine whether symptom exaggeration is a factor in complaints of cognitive dysfunction using 2 new validated instruments in patients with fibromyalgia (FM). METHODS: Ninety-six patients with FM and 16 patients with rheumatoid arthritis (RA) were administered 2 effort or symptom validity tests designed to detect exaggerated memory complaints as part of a battery of psychological tests and self-report questionnaires. RESULTS: A large percentage of patients with FM who were on or seeking disability benefits failed the effort tests. Only 2 patients with FM who were working and/or not claiming disability benefits and no patient with RA scored below the cutoffs for exaggeration of memory difficulties. CONCLUSION: This study illustrates the importance of assessing for exaggeration of cognitive symptoms and biased responding in patients with FM presenting for disability related evaluations.

Prenatal ultrasound evaluation of fetal diastematomyelia: two cases of type I split cord malformation.

Isolated diastematomyelia is a rare form of spinal dysraphism characterized by a sagittal cleft in the spinal cord, conus medullaris and/or filum terminale with splaying of the posterior vertebral elements. This condition is the result of the presence of an osseous or fibrocartilaginous septum producing a complete or incomplete sagittal division of the spinal cord into two hemicords. It may be isolated or associated with other segmental anomalies of the vertebral bodies. Prenatal diagnosis of this anomaly is possible in the early midtrimester by sonography, thus allowing for early surgical intervention and a favorable prognosis. Two cases of fetal diastematomyelia diagnosed by prenatal sonography are presented, each demonstrating the typical sonographic features diagnostic of this condition. The first case, detected at 28 weeks' gestation, presented with disorganization of the bony processes of the vertebral column with a midline echogenic focus. The second fetus, diagnosed at 17 weeks' gestation, had a similar appearance with widening of the posterior elements and the presence of a midline echogenic bony spur. Postnatally, both infants underwent magnetic resonance imaging for a definitive diagnosis. Surgical repair of the defect was performed in the neonatal period in both cases.

Gender differences in factor structure of the Self-Administered Alcoholism Screening Test.

Recent studies have revealed differences between men and women alcoholics in symptoms, consequences, and help-seeking behavior related to alcohol usage. Based on these findings, it was hypothesized that gender differences also would appear on alcohol screening instruments. The Self-Administered Alcoholism Screening Test (Colligan, Davis, & Morse, 1988: SAAST: Swenson & Morse, 1975) of 1,920 men and 1,775 women was subjected to a within-gender, principle-components, factor analysis with a varimax rotation. Gender differences at the component level were revealed. Men endorsed the "help-seeking for alcohol-related problems" component while women endorsed the "help-seeking for emotional problems" component. In addition, men expressed concern about receiving a psychiatric label while women expressed concern about receiving a drinker label. The results suggest that different items need to be used in screening women for alcohol-related problems.

Trends in the prevalence of congenital heart disease: comprehensive observations over a 24-year period in a defined region of Canada.

OBJECTIVE: To determine the prevalence of congenital heart disease (CHD) in the three Maritime provinces, and to study prevalence differences among provinces and defined regions within these provinces. DESIGN: Each province was divided by counties into regions. All cases of CHD who were born alive in the study area between 1966 and 1989 were entered in a registry. Prevalences were analyzed for each province and for selected regions per year, per 1000 live births, and by diagnosis made by one year of age and by the 16th birthday. Comparison was then made with prevalences of a group who had severe lesions. INTERVENTIONS: Excepting a small number of CHD cases who were diagnosed by autopsy only, diagnosis was made by pediatric cardiologists using appropriate procedures, including cardiac ultrasound and cardiac catheterization. SETTING: The only tertiary care centre for children's heart disease in the provinces of Nova Scotia, New Brunswick and Prince Edward Island, areas of relative geographic isolation (combined population of 1.75 million people). MAIN RESULTS: A statistically significant positive linear trend occurred in these provinces during the study. The recorded prevalence of CHD in New Brunswick was significantly lower. Pooled prevalences by the first and 16th birthdays (8.0 and 12.5 per 1000 live births, respectively) of two regions of highest prevalence for 1980-86 were significantly higher (P < 0.05) than the pooled prevalence rate of all the remaining regions. Prevalence rates of a group with severe lesions were stable for 1976-86 in all regions. CONCLUSIONS: Differences in prevalence of CHD among provinces and regions were related to ascertainment levels. Prevalence of CHD with diagnosis by the first and 16th birthdays were approximately 8.0 and 12.5 per 1000 live births, respectively. The prevalence rate of a severe lesion group was a stable measure.

Flow cytometric enumeration of colonies for in vitro chemotherapeutic drug evaluation.

The percentage of 50-100 micron colonies formed by LX-T cells in medium containing agarose was determined microscopically, and this value was compared with the percentage determined by a flow cytometric method based on the forward and 90 degree light scatter of the colonies. As assessed by both in vitro methods, LX-T cells exposed to chemotherapeutic agents formed fewer colonies as the drug concentration increased. However, flow cytometric analysis indicated that a change in the number of colonies formed was a consequence of changing chemotherapeutic drug concentration, whereas microscopic colony counting did not always detect the corresponding change in colony number. These experiments demonstrate that measurement of a drug's chemotherapeutic potential by flow cytometric counting of colonies is an alternative to the enumeration of colonies microscopically.

A double-blind study of prazosin in the treatment of Raynaud's phenomenon in scleroderma.

Nineteen patients with Raynaud's phenomenon in conjunction with progressive systemic sclerosis were given either prazosin hydrochloride (1 mg orally three times a day) or a placebo for eight weeks, after which the treatment procedure was reversed for four weeks. Prazosin was shown to be effective in reducing both the frequency and the severity of vasospasm reported by the patients.

Slow infusion of vinca alkaloids in the treatment of idiopathic thrombocytopenic purpura.

Vinca alkaloids are useful in the treatment of idiopathic thrombocytopenic purpura, a disorder in which macrophages remove platelets sensitized with antibody. Because vinca alkaloids avidly bind to platelets, drugs can be delivered selectively to macrophages. However, drugs given by bolus injection are cleared too rapidly to bind optimally to autologous platelets, and the use of allogeneic platelets loaded with drug in vitro is cumbersome, expensive, and dangerous. Therefore, slow infusions were devised to prolong the duration of enhanced plasma drug concentrations, thereby providing better conditions for in-vivo drug loading into autologous platelets. Twenty-four patients with refractory idiopathic thrombocytopenic purpura were given slow infusions; 17 had good to excellent responses. Eleven of eighteen patients who had been treated with bolus injections had better results when treated with slow infusions. Patients with improved responses had slower plasma clearance rates than did patients with poor responses. Slow infusion therapy had fewer side effects than bolus injection therapy. Slow infusions are the best method for long-term management.

Intra-arterial reserpine for Raynaud's syndrome. Systemic reactions without therapeutic benefit.

Twenty-four patients classified as having Raynaud's disease or Raynaud's phenomenon were given bilateral brachial artery injections of reserpine or saline in a double-blind fashion. In the six weeks following injection, there was no indication that reserpine produced clinical improvement or changed vasomotor reactivity in the treated patients. However, intra-arterial reserpine did produce systemic cardiovascular effects lasting up to six weeks. It is concluded that intra-arterial reserpine as used in this study is an ineffective treatment for Raynaud's disease or Raynaud's phenomenon and may have significant adverse effects.

Neuroendocrine response to cold in Raynaud's syndrome.

Eleven patients with Raynaud's syndrome accompanied by monospecific IgG ANA, nine patients with Raynaud's syndrome in the absence of ANA, and nine normal volunteers were exposed to an ambient cold challenge during which time venous blood was continuously sampled. ANA negative patients were shown to have significantly higher levels of cortisol during a cold challenge than either ANA positive patients or normal controls, and exhibited significantly lower levels of plasma norepinephrine compared with normal controls. ANA positive patients did not differ significantly from normals in their neuroendocrine response to cold. It is suggested that the high plasma cortisol found in Raynaud's syndrome in the absence of ANA may be responsible for the vasospasticity in this group of patients.

Pharmacokinetic principles of antineoplastic drug therapy.

Determinants of host-drug interaction comprise a complex of potentially variable factors. The complexity of this variability compromises the forecasting of favorable response in individual patients given standard therapy. Substantial success with current forms of chemotherapy may require that biochemical, pharmacologic, and clinical profiles be established for each cancer patient whereby the use of drug and drug combination can be rationally applied. The significance of evaluating clinical pharmacokinetic parameters in patients with cancer is placed in perspective with other factors relevant to individual drug response.

Combination chemotherapy of the epipodophyllotoxin derivatives, teniposide and etoposide. A pharmacodynamic rationale?

Previous studies in vitro on the influence of extracellular protein binding of Teniposide (VM26) and Etoposide (VP16-213) on subsequent cellular uptake by experimental murine tumor cells [Cancer Res 38:2549 (1978); Drug Metab Rev 8:119 (1978)] suggested that a timed-sequential combination of VM26 and VP16-213 may increase the bioavailability of VP16-213. This was studied clinically in six cancer patients with ascites (five ovarian, one rectal) whereby VM26 (20 mg/m2) was given i.p. 2 h prior to VP16-213 (100 mg/m2; i.p.) In some patients, this regimen was administered i.v. The i.v. regimen was found to be more toxic (myelosuppression, nausea, vomiting) than i.p. regimen at same doses of drugs. Several patients remained stable to disease during 1-2 courses of therapy (3 weeks per course), one patient had partial remission, and has been stable in her disease for more than 4 months. In two patients, plasma and ascites fluid was analyzed for VP16-213 and VM26 by a new reverse-phase high performance liquid chromatography method. Both VM26 and VP16-213 could be eluted isocratically (28% v/v acetonitrile in water) from a c18 column with retention times of 6.6 and 13.3 min, respectively. Subsequent pharmacokinetic analysis of one patient suggests that protein binding displacement of VP16-213 in plasma and perhaps ascites fluid increased the pharmacokinetic volume of distribution (28 l) and reduced the elimination half-life (12 h). The data suggests that VP16-213 is distributed more widely in the body and is represented by a single compartment pharmacokinetic model. Analysis of VM26 in ascites and plasma suggests that the so-called "deep pharmacokinetic compartment" represents ascites equivalent space and that the plasma concentration represents VM26 as free and protein-bound drug in kinetic distinguishable compartments. Determinants of drug action are potentially composed of a multiplicity of physiological, biochemical, and other factors. The potential for manipulating the pharmacodynamic properties of drugs to achieve greater therapeutic potential needs further study.