Ganser symptoms in a case of frontal-temporal lobe dementia: is there a common neural substrate?

Neuropsychological testing was completed in a patient who showed cognitive decline of mental functions, unusual answers to questions, and other characteristics of what has typically been described in the literature as the "Ganser Syndrome." Clear evidence of malingering on a memory test seemed to confirm that this patient was exaggerating deficits for psychiatric reasons or secondary gain, yet the patient showed evidence of mild organic impairment on MRI and continued to deteriorate in cognitive functions and basic self-care. Although an initial SPECT scan had suggested a pattern inconsistent with dementia, a second scan showed frontal-temporal perfusion deficits. Based on this scan and the clinical picture of progressive deterioration, a diagnosis of frontal-temporal lobe dementia was made. This case illustrates that the seemingly deliberate selection of incorrect responses may occur in the early stages of an organic dementia, and that a diagnosis of frontal-temporal lobe dementia should be considered in cases where symptoms appear to be psychiatric or nonorganic. The case further raises the question of whether the reported symptoms of Ganser Syndrome may be accounted for by frontal-temporal lobe dysfunction, since there appears to be some overlap between symptoms of Ganser Syndrome and frontal-temporal lobe dementia. It is also important to note that many reported cases of Ganser Syndrome had a history of head injury.     

Brain natriuretic peptide (nesiritide) in the treatment of heart failure

Over the last decade brain natriuretic peptide (BNP) emerged as a cardiac hormone of clinical interest in diagnosis, prognosis and treatment of patients with Heart Failure (HF). The diagnostic potential of BNP is now well established both in patients with suspected HF as well as in patients with asymptomatic left ventricular systolic dysfunction. The prognostic information obtained from BNP levels in HF and acute myocardial infarction patients seems even more promising. Nesiritide is a synthetic peptide, homologous to endogenous BNP. It is a balanced vasodilator with diuretic and natriuretic properties. It decreases the elevated levels of neurohormones resulting from activation of the sympathetic and renin-aldosterone systems in HF. The results of clinical trials involving more than 2000 patients with decompensated HF are now available. In these trials nesiritide was administered by single or repeated bolus injections, as well as by sustained infusions. Nesiritide has been shown to produce a potent, dose-related vasodilator effect that is rapid in onset and sustained during infusion. Balanced vasodilation is reflected by decreases in systemic vascular resistance, pulmonary artery wedge pressure and right atrial pressure. No tachyphylaxis has been observed in these trials. Efficacy of nesiritide in the treatment of decompensated HF has been demonstrated. Trials comparing nesiritide with conventional treatment of decompensated HF showed that nesiritide compares favorably to standard agents. The safety profile has been excellent with a dose-dependent hypotension as the major side effect. Ventricular arrhythmia was not more frequent in patients treated with nesiritide than with placebo. Thus, nesiritide appears to be useful as a first-line agent in the treatment of patients with decompensated HF.     

Energy restriction-induced changes in body composition are age specific in mice

Restricting energy intake while supplying adequate micronutrients slows aging and extends maximal lifespan, whereas loss of body weight with exercise training does not. Our goal was to test the hypothesis that weight loss via energy restriction (ER) alters body composition in a way that is: 1) distinct from exercise-induced weight loss; and 2) conserved regardless of the age at which ER is initiated. An experimental model was developed where matched losses in weight could be induced with 6 mo of ER (approximately 55% of ad libitum energy intake) or voluntary exercise on a running wheel in adult (12 mo) male C57BL/6 mice and a similar amount of ER-induced weight loss could be induced in aged mice (24 mo). Using dual-energy X-ray absorptiometry, we determined that ER and exercise in the 12-mo-old mice caused nearly identical changes in the amount and distribution of adipose tissue in the 12-mo group, with 70-75% of overall weight loss due to fat loss. Decreased prostate and epididymal fat weights were similar with ER and exercise, and heart weight was unaffected by either intervention. In contrast to the adult mice, in aged mice, ER caused primarily a loss of lean body mass including the heart, with no decreased prostate or fat pad weight. Bone mineral density was decreased by ER but not exercise in the adult mice, an effect not seen in the aged mice. Our data refute the hypothesis that ER causes a unique change in body composition that is conserved across age and suggest that fat loss may not be an essential component of the anti-aging effects of ER.     

Prognosis in patients with heart failure and preserved left ventricular systolic function.

BACKGROUND: It is recognized that heart failure patients with preserved left ventricular systolic function have better prognosis; nevertheless, there are some studies with conflicting results. Also, there is a paucity of data concerning the prognostic factors in this group of patients. OBJECTIVES: To determine possible variables with prognostic relevance in heart failure patients with preserved left ventricular systolic function (ejection fraction > 40%). METHODS: 157 consecutive ambulatory patients with heart failure were assessed; those patients with ejection fraction > 40% were included in the study (n = 46). All patients were evaluated by clinical interview and physical examination, ECG, echocardiogram (M-mode, 2D and pulsed Doppler of mitral flow), biochemical study and determination of type B natriuretic peptide (BNP). The patients were grouped according to the rhythm presented on ECG: Group I--patients with atrial fibrillation; Group II--patients in sinus rhythm Group II was further subdivided in two groups according to the presence or absence of restrictive left ventricular filling pattern. All patients had a clinical follow-up, with recording of events (death or hospitalization from cardiac cause). The mean follow-up time was 682.2 +/- 55 days. RESULTS: The mean age of the patients was 70.4 +/- 1.2 years; 54.3% were women; mean ejection fraction was 49.6 +/- 1%; mean BNP levels were 202.9 +/- 41.3 pg/ml. Mortality was 19.6% and the combined event death or hospitalization from cardiac cause) occurred in 26.1% of the patients. Among the clinical, demographic, biochemical, echocardiographic and neurohumoral parameters, only BNP levels had prognostic significance in the whole population. In Group II patients, BNP levels, heart rate and restrictive left ventricular filling pattern were identified as having prognostic significance. Kaplan-Meyer curve analysis showed that both BNP and restrictive left ventricular filling pattern seemed to be important prognostic markers. CONCLUSIONS: This preliminary study suggests thar neurohumoral activity (determined by plasma BNP levels) and a restrictive ventricular filling pattern may be important factors in prognostic stratification of heart failure patients with preserved left ventricular systolic function.     

A neonatal swine model for peanut allergy.

BACKGROUND: Peanut allergy represents a significant health threat in the United States. The factors contributing to the severity of the allergic response and the immunopathogenic mechanisms underlying peanut allergy remain to be completely characterized. As yet, no animal model has been developed that will completely mimic the physical, immunologic, and histologic features of food allergy. OBJECTIVE: The purpose of this investigation was to develop a neonatal pig model of peanut allergy that would mimic the allergic symptoms and the immunologic and histologic profile of human peanut allergy. METHODS: Newborn piglets sensitized intraperitoneally with peanut extract and cholera toxin were orally challenged repeatedly with peanut meal. Physical symptoms, including emesis, lethargy, diarrhea, and respiratory distress, were monitored to determine the allergic response. Immunologic assessment was conducted through use of skin testing and the antigenic response to peanut proteins. Histologically, tissues derived from the esophagus, stomach, small intestine, and colon were assessed for morphologic changes after the oral challenge. RESULTS: Peanut-sensitized pigs responded with physical symptoms that mimicked those seen in double-blinded, placebo-controlled oral food challenges to peanuts in children and adults. Skin testing suggested an IgE-mediated response; this was confirmed by a negative passive cutaneous anaphylaxis response of heat-treated sera obtained from peanut-sensitized animals. Damage to villi of the small intestine was similar to that seen in endoscopically obtained tissue specimens from certain food-allergic individuals. CONCLUSION: The neonatal pig model of peanut allergy mimics the physical and immunologic characteristics of peanut allergy in human beings. The model will be useful for determining IgE-mediated mechanisms and conducting endoscopic histologic assessment of tissues and immunotherapeutic intervention strategies with repeated allergen challenges.     

Evaluation of the Simple Calculated Osteoporosis Risk Estimation (SCORE) in Older Caucasian Women: The Rancho Bernardo Study

Osteoporosis is a major health problem in older women. A risk assessment tool, the Simple Calculated Osteoporosis Risk Estimation (SCORE), has been developed to identify postmenopausal women likely to have low bone mass who should be referred for bone densitometry. The objective of this study was to calculate the sensitivity, specificity and predictive values of SCORE in a community-dwelling sample of older women. A total of 1013 postmenopausal Caucasian women aged 44–98 years provided a standard medical history including history of osteoporotic fractures and medication use. Bone mineral density (BMD) was measured at the femoral neck using dual-energy X-ray absorptiometry. In accordance with the SCORE protocol, low BMD was defined as 2 or more standard deviations below the mean BMD in healthy young women. Among these older women (mean age = 72.5 years), 67% had low BMD. Using the recommended SCORE cutpoint of 6, the sensitivity of SCORE was 98% but the specificity was only 12.5%. The positive predictive value (PPV) and negative predictive value (NPV) were 69% and 75%, respectively, meaning that all but 5.5% of the women would be recommended for bone densitometry. Increasing the cutpoint of 11, based on ethnicity and the receiver operating characteristic (ROC) curve, reduced sensitivity to 80% but improved specificity to 46%. The PPV and NPV were 75% and 53%, respectively, meaning that bone scans would not be recommended for 28% of the women. However, 13% of the women with low BMD would be missed. Analyses restricted to women <74 years of age reduced the rate of recommended bone densitometry but increased the number of women with low BMD who would be missed. We conclude that SCORE has limited value as a method for appropriately referring older ambulatory women for bone densitometry. Received: 28 December 1998 / Accepted: 30 December 1998     

BDNF and extracellular matrix regulate differentiation of mice neurosphere‐derived cells into a GABAergic neuronal phenotype

Differentiation of neurosphere‐derived cells is regulated by extracellular cues, namely, growth factors and proteins of the extracellular matrix (ECM). In this study we analyzed the influence of nerve growth factor (NGF), brain‐derived neurotrophic factor (BDNF), retinoic acid plus potassium chloride (RA‐KCl), and the nonsynthetic ECMs laminin (LN) and fibronectin (FN) versus the synthetic adhesion substrate poly‐L ‐lysine (PLL) in the in vitro differentiation of postnatal neurosphere cells. BDNF increased the number of differentiated neurons and decreased the number of neuronal precursors (nestin‐positive cells) compared with NGF or RA‐KCl. Moreover, cells treated with BDNF plus B27 supplement acquired a γ‐aminobutyric acid (GABA)–ergic phenotype and showed increased survival. No significant differences were found in the number of differentiated neurons in the presence of the ECMs alone. Nevertheless, FN or PLL in combination with BDNF promoted the acquisition of a GABAergic phenotype. The results obtained in this study highlight the importance of growth factors and ECM proteins for the potential of neurosphere cells to differentiate into neurons. © 2009 Wiley‐Liss, Inc.