Relevance of 10-min delayed recall in dementia screening

Within the context of early diagnosis of Alzheimer's disease (AD), there is a growing interest in neuropsychological screening tests. Amongst these tests, we focused on the largely used Memory Impairment Screen (MIS). The objective of the present work was to show that adding a 10-min delayed recall to the MIS, improves the test psychometric characteristics in order to detect dementia in the earliest stages. A prospective study was carried out on a cohort of 270 consecutive elderly ambulatory subjects attending the Broca Hospital Memory Clinic: normal controls ( n  = 67), mild cognitive impairment subjects ( n  = 98) and mildly demented patients [ n  = 105, Mini Mental State Examination (MMSE) = 23 ± 4]. This study consisted in testing the advantage of the 10-min delayed recall entitled MIS-D compared with the MIS. At a cut-off score of 6, the MIS-D revealed satisfying psychometric characteristics with a sensitivity of 81% and a specificity of 91%, whilst the MIS alone indicated a sensitivity of 60% and a specificity of 88% in detecting dementia. In demented patients with MMSE score ≥26, MIS-D properties still remained satisfying (sensitivity: 75%, specificity: 92%). MIS-D is a more relevant screening test than MIS alone at very early stages of dementia.     

Contribution of Calcium Channel Subtypes to the Intracellular Calcium Signal in Sensory Neurons: The Effect of Injury

Background: Although the activation-induced intracellular Ca2+ signal is disrupted by sensory neuron injury, the contribution of specific Ca2+ channel subtypes is unknown.

Methods: Transients in dissociated rat dorsal root ganglion neurons were recorded using fura-2 microfluorometry. Neurons from control rats and from neuropathic animals after spinal nerve ligation were activated either by elevated bath K+ or by field stimulation. Transients were compared before and after application of selective blockers of voltage-activated Ca2+ channel subtypes.

Results: Transient amplitude and area were decreased by blockade of the L-type channel, particularly during sustained K+ stimulation. Significant contributions to the Ca2+ transient are attributable to the N-, P/Q-, and R-type channels, especially in small neurons. Results for T-type blockade varied widely between cells. After injury, transients lost sensitivity to N-type and R-type blockers in axotomized small neurons, whereas adjacent small neurons showed decreased responses to blockers of R-type channels. Axotomized large neurons were less sensitive to blockade of N- and P/Q-type channels. After injury, neurons adjacent to axotomy show decreased sensitivity of K+-induced transients to L-type blockade but increased sensitivity during field stimulation.     

Muscarinic cholinergic and alpha 2-adrenergic receptors in the epithelium and muscularis of the human ileum

The aim of this study was to characterize the binding and functional properties of muscarinic cholinergic (MCh) and alpha 2-adrenergic receptors in the human ileum to provide insight into pharmacologic strategies for managing urinary and fecal incontinence after bladder and rectal replacement with intestinal segments. MCh and alpha 2-adrenergic binding sites were characterized in the epithelium and muscularis of eight human ileal segments with 3H-N-methylscopolamine and 3H-rauwolscine, respectively. The dissociation constant for 3H-N-methylscopolamine in the epithelium and muscularis was 0.32 +/- 0.07 nmol/L and 0.45 +/- 0.10 nmol/L, respectively (p = 0.32). The MCh receptor content was approximately eightfold greater in the muscularis compared with the epithelium (p = 0.008). The dissociation constant for 3H-rauwolscine in the muscularis and epithelium was 2.55 +/- 0.42 nmol/L and 2.03 +/- 0.19 nmol/L, respectively (p = 0.29). The alpha 2-adrenoceptor density was twofold greater in the epithelium compared with the muscularis (p = 0.05). Noncumulative concentration-response experiments were performed with carbachol, an MCh agonist, and UK-14304, a selective alpha 2-adrenergic agonist. The epithelium did not contract in the presence of high concentrations of carbachol and UK-14304. The muscularis preparations were responsive only to carbachol. The muscularis contains primarily MCh receptors mediating smooth muscle contraction. The alpha 2-adrenoceptors are localized primarily to the epithelium and may regulate water secretion in the intestine. The distribution and functional properties of ileal MCh and alpha 2-adrenergic receptors provide a theoretic basis for the treatment of incontinence after bladder and rectal replacement with intestinal segments.     

Composantes neurosensorielles et hormonales dans l’anorexie mentale

Anorexia nervosa (AN) is often considered a multifactorial illness of unknown pathophysiology. Family and twin studies have consistently demonstrated that AN is strongly related to genetic factors. The probability of some genetic origin is 92%, genetic factors explaining around 20% of the variance. It must be remembered that 95% of the AN patients were girls or women, suggesting a role for gonadal hormonal systems and their effects on the brain and on cognitive functions. Most studies focused on the serotonin system, but other candidate genes have been suggested. At the present time, we have no evidence that women who develop AN have an adipose, metabolic, gonadal, pituitary, hypothalamic or some other dysfunctions that predispose them for the illness. It is suggested on the contrary that the symptoms of AN are physiological responses to starvation or to the response to altered body image and self-satisfaction. If this eating disorder is related to the fear of the alimentary desire of the patients, it will be easy to understand the plasma level of adiponectin, ghrelin and better understand a role for the low leptin level in the enhanced hunger. If we remember that almost 60% of these patients are engaged in a physical and mental hyperactivity, the abnormality in plasma level of cortisol, ACTH, and CRH. The decease in fat mass could explain why leptin level was low and low leptin level may explain the amenorrhea and the fall in LH, FSH, and LH–RH secretion. Moreover, anxiety, obsessive compulsive disorders and physical hyperactivity may be three interrelated factors, which could be related to serotonin and dopamine systems and in turn inhibit food intake.     

The efficacy of transurethral resection of the prostate in men with moderate symptoms of prostatism.

Transurethral resection of the prostate represents the operation most commonly performed by urologists in the United States. The objective of this study was to determine the efficacy of transurethral prostatectomy in men with moderate symptoms of prostatism. The efficacy parameters evaluated included peak urinary flow rate, obstructive and irritative symptom scores, and the global assessment by the patient of the voiding symptomatology. The mean peak urinary flow rate improved 108% after transurethral prostatectomy, and the mean obstructive and irritative symptom scores decreased 88 and 65%, respectively. The observed changes in urinary flow rates and symptom scores were statistically and clinically significant. Over-all, 84% of the patients indicated that the voiding symptoms were markedly improved after prostatic resection. Baseline urodynamic parameters were of no value for prediction of postoperative outcome. Several investigators recently reported their clinical experience with various pharmacological approaches for the treatment of symptomatic benign prostatic hyperplasia. Over-all, the degree of improvement in urinary flow rates and symptom scores achieved after transurethral prostatectomy exceeds all other therapeutic options that presently are available for the treatment of benign prostatic hyperplasia.     

Late Ureteral Stenosis Following Renal Transplantation: Risk Factors and Impact on Patient and Graft Survival

The aim of this retrospective study of a cohort of 1787 consecutive kidney transplantations was to analyze the risk factors associated with the occurrence of ureteral stenosis and the impact of ureteral stenosis on graft and patient survival. Between January 1990 and December 2002, 1787 renal transplantations were performed at our center. Only stenosis observed after the first month, were considered. Among the parameters studied were: donor age and serum creatinine before procurement; recipient age, cold ischemia time, delayed graft function (DGF), number of arteries and the presence of a double J stent. The follow-up parameters were the number and timing of acute rejection episodes, cytomegalovirus (CMV) infection, acute pyelonephritis, renal function and death. Ureteral stenosis occurred in 4.1% of patients and was correlated with donor age > 65 years (p = 0.001), kidneys with more than 2 arteries (p = 0.009) and DGF (p = 0.016). Ureteral stenosis did not affect 10-year patient and graft survival rates, which were respectively 90% and 64% for the stenosis group, 86% and 63% for the no-stenosis group (p = NS). These data suggest an important role for donor age, number of renal arteries and DGF for the occurrence of ureteral stenosis following renal transplantation.     

Release of platelet-activating factor (PAF-acether) and arachidonic acid metabolites from alveolar macrophages

Human, monkey and rat alveolar macrophages (AM) release PAF-acether in a dose-dependent fashion in the presence of 1 to 5 g/ml ionophore A 23187 (2.5 pmol of PAF-acether from 2.5×10⁵ cells) but not in the presence of zymosan. Arachidonic acid (AA) metabolites released from AM from these species were studied. Thromboxane A₂ TxA₂)—detected by its action on rabbit arteries—was released from human, monkey and rat AM upon addition of 0.5 mM AA. This release was inhibited by aspirin and indomethacin. Lipoxygenase and cyclooxygenase AA metabolites from rat AM were identified using high efficiency glass capillary column gas chromatography coupled to mass spectrometry. The cyclooxygenase metabolites PGF₂, E₂ and D₂ and TxB₂ were identified. The lipoxygenase-dependent AA metabolites were explored using aspirin-pretreated AM. Only 12 HETE was found.These data indicate that AM secrete several substances with bronchoconstrictive activity: PGF₂, D₂, TxA₂ and PAF-acether. Therefore an active role of AM in human and experimental bronchoconstriction must be considered.     

Effects of 15-hydroperoxyeicosatetraenoic acid on human lymphocyte sheep erythrocyte rosette formation and response to concanavalin A associated with HLA system

The lipoxygenase product hydroperoxyeicosatetraenoic acid (HPETE) has immunosuppressive properties in vitro and in vivo. It was observed that 15-HPETE inhibit the sheep red blood cell rosette formation and the concanavalin A-induced blast transformation of human lymphocytes. This inhibition was HLA-linked. HLA-B12 subjects were less sensitive than non-B12 subjects. It is likely that HPETE acids are macrophage mediators which inhibit some lymphocyte functions.     

Metastatic cancers of the thyroid gland. Diagnostic difficulties

Metastatic carcinoma of the thyroid is uncommon in surgical pathology and may masquerade as primary thyroid cancer. We studied 6 cases of biopsied and/or surgically resected metastatic carcinoma of the thyroid and their corresponding primary carcinoma, with emphasis on the differential diagnosis. There were 4 men and 2 women patients aged 44 to 77. The primary carcinoma was a breast infiltrating duct carcinoma (3 cases), a colorectal adenocarcinoma (2 cases) and a bronchial oat-cell carcinoma (1 case). The interval between primary carcinoma and secondary thyroid carcinoma was 2 to 9 years in 4 cases; 2 other cases showed simultaneous occurrence. Five patients died with widespread metastases 1 to 14 months following the diagnosis of secondary carcinoma of the thyroid; 1 patient was alive after 24 months. The histological differentiation of secondary from primary thyroid cancer may be difficult in the following situations: clear-cell, Hürthle-cell and signet ring cell changes; positivity of mucins stains; production of melanin; epidermoid differentiation; very rare miscellaneous tumours ("columnar cell carcinoma" and primary thymoma of the thyroid). Immunoperoxidase methods and mucin histochemistry may help.     

Management of behavioral disorders in dementia patients

Behavioral disorders are major manifestations of Alzheimer's disease and other forms of dementia. They are associated with caregiver distress, increase the likelihood of institutionalization and may be associated with more rapid cognitive decline. The first step of treatment strategy is an assessment of these disorders. Treatment of behavioral signs is an etiological treatment. Acute behavioral signs are often related to an unknown somatic disease. Chronic signs are often symptoms of the neurological dementia and can be reduced, especially by serotonergic agents and anticonvulsivants. The new antipsychotics are a good alternative to classic neuroleptics known for their frequent cognitive side effects in demented patients. Anticholinesterasic drugs can positively influence noncognitive signs. The treatment of behavioral and psychological symptoms of dementia (BPSD) involves a number of specific interventions including cognitive stimulation which has shown effectiveness on both cognitive functions and quality of life. Prevention of BPSD includes safety measures such as evaluation of suicidality and violence, vigilance regarding neglect and abuse, planning for legal issues due to the patient's incapacity. Families or caregivers should be provided with counseling, education and support. The treatment of BPSD is part of a global and multimodal care which involves general practioners, nurses, social workers, physiotherapists, neuropsychologists, speech therapists, memory centers, psychogeriatric and geriatric units, and respite care units, nursing homes and long-term care facilities. The coordination of the professionals is a critical aspect of providing effective care for patients with Alzheimer's disease.