Thinning of the cerebral cortex in aging

The thickness of the cerebral cortex was measured in 106 non-demented participants ranging in age from 18 to 93 years. For each participant, multiple acquisitions of structural T1-weighted magnetic resonance imaging (MRI) scans were averaged to yield high-resolution, high-contrast data sets. Cortical thickness was estimated as the distance between the gray/white boundary and the outer cortical surface, resulting in a continuous estimate across the cortical mantle. Global thinning was apparent by middle age. Men and women showed a similar degree of global thinning, and did not differ in mean thickness in the younger or older groups. Age-associated differences were widespread but demonstrated a patchwork of regional atrophy and sparing. Examination of subsets of the data from independent samples produced highly similar age-associated patterns of atrophy, suggesting that the specific anatomic patterns within the maps were reliable. Certain results, including prominent atrophy of prefrontal cortex and relative sparing of temporal and parahippocampal cortex, converged with previous findings. Other results were unexpected, such as the finding of prominent atrophy in frontal cortex near primary motor cortex and calcarine cortex near primary visual cortex. These findings demonstrate that cortical thinning occurs by middle age and spans widespread cortical regions that include primary as well as association cortex.     

Unruptured aneurysm of the middle cerebral artery presenting with psychomotor seizures: case study and review of the literature

An intracranial aneurysm would be low on the differential diagnosis of a patient presenting with behavioral or emotional changes. Nonetheless, complex partial seizures (CPS) may cause such symptoms and result from an unruptured intracranial aneurysm. Failure to diagnose and treat this condition in a timely manner increases the patient's risk of catastrophic aneurysmal rupture. This report describes a 55-year-old woman who presented following two CPS which began with the perception of a strange smell and culminated in a brief loss of consciousness. She had no history of seizure disorder or recent trauma. Magnetic resonance imaging (MRI) revealed a space-occupying lesion over the right temporal lobe near the amygdala. Magnetic resonance angiography (MRA) confirmed a 1.5-cm right middle cerebral artery aneurysm, with a dome projecting toward the amygdalohippocampal region. Following surgical ablation, the patient's CPS were well controlled. A review of the literature is performed on this unusual etiology and management strategies are discussed.     

Promising treatments for women with comorbid PTSD and substance use disorders

OBJECTIVE: The authors' goal was to compare the efficacy of a manualized cognitive behavior therapy that addresses both posttraumatic stress disorder (PTSD) and substance abuse (seeking safety) with a manualized cognitive behavior therapy that addresses only substance abuse (relapse prevention) and with standard community care for the treatment of comorbid posttraumatic stress disorder (PTSD) and substance use disorder. METHOD: One hundred seven women from an urban, low-income population who had comorbid PTSD and substance use disorder were randomly assigned to receive the two kinds of cognitive behavior therapy or received standard community treatment. Participants were recruited from both community and clinical populations and evaluated with structured clinical instruments. Forty-one women received seeking safety therapy, 34 received relapse prevention therapy, and 32 received standard community care. RESULTS: At the end of 3 months of treatment, participants in both cognitive behavior therapy conditions had significant reductions in substance use, PTSD, and psychiatric symptoms, but community care participants worsened over time. Both groups receiving cognitive behavior therapy sustained greater improvement in substance use and PTSD symptoms at 6-month and 9-month follow-ups than subjects in the community care group. CONCLUSIONS: Seeking safety and relapse prevention are efficacious short-term treatments for low-income urban women with PTSD, substance use disorder, and other psychiatric symptoms.     

13C-breath tests in the study of mitochondrial liver function

Breath tests for "dynamic" liver function evaluation have been proposed several years ago. A variety of carbon-labelled breath tests for the assessment of mitochondrial, microsomal and cytosolic liver function have been described with the aim to increase data on liver disease staging, prognosis, and response to therapy. In the last years a great interest is developed about the use of breath test for liver mitochondrial function evaluation since it results impaired in a wide range of liver diseases either of genetic or acquired origin. In these cases mitochondrial oxidative metabolism of some substrates, as far as recovery of the hepatic energy state after a metabolic insult, results impaired because of the disfunction of the electron transport chain and/or ATP synthesis. Ketoisocaproic acid and methionine are the best studied carbon-labelled substrates for the investigation of mitochondrial functional damages related to structural alterations that occur in many liver diseases. Although these tests are simple, cost-effective and safe, to date there is still not general approval for their usefulness in clinical settings since they should fulfill several requirements to overcome the drawbacks of traditional quantitative tests. On the other hand, this field is relatively young and further studies are needed in order to assess the suitable substrate for the evaluation of the complex mitochondrial metabolism both in healthy subjects and in patients with liver disease.     

Unilateral endolymphatic hydrops: what about the contralateral ear?

INTRODUCTION: The early recognition of incipient Meniere's disease (MD) in the asymptomatic ear of a patient with known unilateral disease has profound implications for patient management and follow-up, but the criteria for a right and precocious diagnosis is still controversial. MATERIALS AND METHODS: We evaluated forty-nine patients with MD, selected according to Committee on Hearing and Equilibrium guidelines. All patients underwent laminar tonal audiometry, stapedial reflex study, Glycerol dehydration test, Auditory Brainstem Response (ABR) vestibular examination. MRI was performed in 14 patients. RESULTS: A raised hearing threshold in the contralateral ear was found in 27 patients, but only 7 (14.3%) fulfilled the requirements to be considered affected by bilateral MD. The average delay of occurrence in the contralateral ear was 7 years (from 5 to 12 years). The glycerol test was positive only in 4 patients with unilateral MD and moderate hearing loss. It was not positive in any case of bilateral MD. The membranous endolymphatic duct and sac is not well visualised with MRI on the affected side in the majority of patients. CONCLUSION: A MRI study must be included in the diagnostic protocol for MD and with improvements in this imaging modality will possibly allow detection of variations in the size of inner ear structures. Glycerol dehydration test was useful only in selected cases. A full assessment of incipient disease in the asymptomatic ear in unilateral Meniere's disease should be undertaken. A conservative approach in surgical treatment of unilateral MD is recommended because of the possibility of evolution of a bilateral form, which can occur even 10 years after the onset of the disease.     

A study on the role of nitric oxide and iron in 3-morpholino-sydnonimine-induced increases in dopamine release in the striatum of freely moving rats

1. We showed previously that interaction between NO and iron (II), both released following the decomposition of sodium nitroprusside (SNP), accounted for the late SNP-induced dopamine (DA) increase in dialysates from the striatum of freely moving rats; in addition, we showed that co-infusion of iron (II) with the NO-donor S-nitroso-N-acetylpenicillamine mimicked SNP effects on striatal DA release. 2. In the present study, intrastriatal co-infusion of iron (II) (given as FeSO(4), 1 mM for 40 min) with the NO-donor and potential peroxynitrite generator 3-morpholinosydnonimine (SIN-1) (0.2, 0.5, 1.0 or 5.0 mM for 180 min), potentiated the SIN-1-induced increase in DA concentration in dialysates from the striatum of freely moving rats. Neither alone nor associated with iron (II) did SIN-1 induce changes in dialysate ascorbic acid or uric acid concentrations. 3. Neither co-infusion of a superoxide dismutase mimetic nor uric acid affected SIN-1-induced increases in dialysate DA concentration. 4. Infusion of the iron chelator deferoxamine (0.2 mM for 180 min) decreased dialysate DA and attenuated SIN-1-induced increases in dialysate DA concentrations. 5. These results suggest that iron plays a key role in SIN-1-induced release of striatal DA and do not support any role for either peroxynitrite or superoxide anion in SIN-1-induced release of striatal DA.     

Breath alkanes determination in ulcerative colitis and Crohn's disease

PURPOSE: By considering the pathophysiologic basis of inflammatory bowel diseases, a role for excessive lipid peroxidation caused by oxygen free radical compounds has been proposed repeatedly. However, to date only a few studies are available on this topic in human beings. This study was designed to assess breath alkanes in a group of patients with active inflammatory bowel disease by a technique that clearly distinguishes pentane from isoprene, to prevent overestimation of values as in previous studies. PATIENTS: Twenty patients with a diagnosis of active inflammatory bowel disease (10 with Crohn's disease and 10 with ulcerative colitis) were studied. Extension of the disease was similar between patient groups, and all were treated with equivalent doses of steroids and salicylates. METHODS: Breath alkanes determination was performed by a standard procedure involving a gas cromatography column able to separate pentane from isoprene. RESULTS: Overall, significant differences between patients with inflammatory bowel diseases and controls were found for ethane, propane, and pentane, but not for butane and isoprene. Isoprene was clearly distinguished from pentane, demonstrating that the significant elevation of pentane levels in patients with inflammatory bowel diseases is a real phenomenon and not an artifact caused by coelution with isoprene. CONCLUSIONS: An excess of lipid peroxidation is probably an important pathogenetic factor in inflammatory bowel diseases, and this may be assessed through a nonivasive method. Because this method previously also has been shown to be able to evaluate disease activity, it could be a useful tool for studying patients with inflammatory bowel diseases.     

Intermale aggression and infanticide in aged C57BL/6J male mice: Behavioral deficits are not related to serum testosterone (T) levels and are not recovered by supplemental T

Healthy aged adul (24–26 months of age) and young adult (2–4 months of age) C57BL/6J male mice were assessed for intermale aggression, pup-killing behavior (infanticide), and circulating levels of testosterone (T). When compared to young adult male mice, aged adult males were highly variable in the exhibition of both androgen-dependent behaviors. Significant numbers of aged males exhibited deficits in aggression and pup-killing while other animals were as behaviorally active as their young male counterparts. Assessment of serum T showed that aging did not produce a reduction in levels of the steroid and individual variability in androgen-dependent behavior of aged males was not related to plasma levels of the hormone. When aged non-aggressive and non-killer males were exposed to supplemental T by way of subcutaneously implanted silastic capsules, circulating levels of the steroid were elevated but T-dependent behavior was not recovered. These findings, in combination with those previously reported for copulatory behavior, indicate that the deficits observed in the androgen-dependent behavior of aged male mice cannot be attributed to a breakdown in the production of testicular androgens. While neural refractoriness to T may account in part for deficits in androgen-dependent behavior of aged males, the variability that is observed in the reproductive behaviors of aged male rodents ultimately may be related to other sources of variation such as perinatal environment.     

Effects of morphine treatment and withdrawal on striatal and limbic monoaminergic activity and ascorbic acid oxidation in the rat

Since ascorbic acid (AA) reportedly suppresses tolerance to and dependence on morphine in humans and rodents, levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3-methoxytyramine (3-MT), 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), AA, dehydroascorbic acid (DHAA), uric acid, xanthine, hypoxanthine, glutamate and γ-amino-butyric acid (GABA) were determined by high-pressure liquid chromatography (HPLC) in the striatum and in the limbic forebrain of the rat following morphine treatment (single or repeated) and withdrawal. Single morphine administration (20 mg/kg s.c.) increased DOPAC + HVA/DA, 5-HIAA/5-HT and DHAA/AA ratios, uric acid levels, and decreased xanthine, hypoxanthine, glutamate and GABA levels in both regions. 3-MT levels were decreased in the striatum and increased in the limbic forebrain. After 7 days of morphine treatment, striatal DOPAC + HVA/DA and DHAA/AA ratios and uric acid levels were still higher and striatal and limbic xanthine levels still lower than in controls, while all other parameters were in the range of control values in both regions. Morphine treatment also increased the glutamate/GABA ratio in the striatum. In all morphine-treated rats, individual striatal DOPAC + HVA/DA and DHAA/AA ratio values were directly correlated. After a 48 h withdrawal period, both striatal AA oxidation and glutamate/GABA ratio further increased; limbic 3-MT levels further decreased, while all other parameters did not differ from control values. We conclude that: (i) tolerance to morphine-induced increase in hypoxanthine, xanthine and AA oxidation develops in the limbic forebrain faster than in the striatum; (ii) the morphine-induced increase in striatal and limbic AA oxidation may be considered a consequence of increased formation of reactive oxygen species due to increased DA, hypoxanthine and xanthine oxidative metabolism; (iii) a striatal excitotoxic imbalance characterizes the withdrawal state and may be taken into account to explain the further increase in striatal AA oxidation.     

Initial results of the reliability and validity of a German-language scale for the quantitative measurement of postoperative pain in young children

In a previous study it was proved impossible to evaluate the validity of a system modified according to McGrath et al. for measuring postoperative pain in children. Three reasons were postulated for this result. The analgesics used did not modulate the pain in such a manner that the statistical analysis was effective; or the postoperative pain had an acute onset or fluctuated and the regular observations did not allow detection of the pain peaks; or the system used did not measure pain. Therefore, a new and different approach was adopted to evaluate the reliability and validity of a scoring system for the measurement of postoperative pain in small children. MATERIAL. Sixty children classed as ASA I and II and aged between 1 and 5 years were randomly allocated to 2 groups: one group received Tramadol (0.5 mg/kg) after the induction of anesthesia and the other group received placebo. Premedication and anesthesia were standardized. All indications were accepted except for urgent operations and painful diseases. For 1 h after the operation the children were continuously observed by an experienced pediatric anesthetist who did not know what drugs had been given. Every 15 min and when the observer was convinced that the children were in pain and needed analgesics the following items were scaled: wakefulness, wake-up reaction, crying, facial expression, position of the trunk, position of the legs, muscle tone, making contact, verbal communication on being asked about pain, special defense against stimuli and consolability. The items were included in a factor analysis (principal components). The number of the factors was detected using the Scree test. The only items accepted as reliable were those that had a substantial load of at least 0.4 at each measurement. The reliability coefficient was computed with the split-half technique (odd-even). The validity was estimated with a multifactorial analysis of variance with repeated measurements. When the observer was convinced that any child was in pain, Metamizol (15 mg/kg) was administered. Significance was assumed at P less than 0.05. The study was accepted by the ethical committee of the Ruhr University, Bochum. RESULTS. A replication verified the results of the previous study: the factor analysis resulted in a one-factorial solution. Of the 8 items (wakefulness, wake-up reactions, crying, position of the trunk, position of the legs, verbal communications on being asked about pain, special defense against stimuli) only 4 had a sufficiently substantial load on all measurements (crying, facial expression, position of the trunk and position of the legs). (ABSTRACT TRUNCATED AT 400 WORDS)