Liatermin did not confer the predetermined level of clinical benefit to patients with PD despite increased (18)F-dopa uptake. It is uncertain whether technical differences between this trial and positive open-label studies contributed in any way this negative outcome.

SYNOPSISA 2¼-year prospective study of children suffering head injury is described. Three groups of children were studied: (a) 31 children with ‘severe’ head injuries resulting in a post-traumatic amnesia (PTA) of at least 7 days; (b) an individually matched control group of 28 children with hospital-treated orthopaedic injuries; and (c) 29 children with ‘mild’ head injuries resulting in a PTA exceeding 1 hour but less than 1 week. A retrospective assessment of the children's pre-accident behaviour was obtained by parental interview and teacher questionnaire immediately after the accident and before the behavioural sequelae of the injury could be known. Further psychiatric assessments were undertaken 4 months, 1 year and 21 years after the initial injury. The mild head injury group showed a raised level of behavioural disturbance before the accident but no increase thereafter. It was concluded that head injuries resulting in a PTA of less than I week did not appreciably increase the psychiatric risk. By contrast, there was a marked increase in psychiatric disorders following severe head injury. The high rate of new disorders in children with severe head injuries who were without disorder before the accident, together with the finding of a dose–response relationship with the severity of brain injury, indicated a causal relationship. However, the development of psychiatric disorders in children with severe head injuries was also influenced by the children's pre-accident behaviour, their intellectual level, and their psychosocial circumstances. With the exception of social disinhibition and a slight tendency for the disorders to show greater persistence over time, the disorders attributable to head injury showed no specific features.

The intrathecal delivery of r-metHuBDNF in doses of up to 150 microg/day was well tolerated and appears feasible. The reversible CNS effects with higher dose indicate that BDNF can be delivered cranially against CSF flow. The small number of patients and the design of the study did not permit conclusions to be drawn about the efficacy of the treatment.

SYNOPSISA 2¼-year prospective study of children suffering head injury is described. Three groups of children were studied: (a) 31 children with ‘severe’ head injuries resulting in a post-traumatic amnesia (PTA) of at least 7 days; (b) an individually matched control group of 28 children with hospital treated orthopaedic injuries; and (c) 29 children with ‘mild’ head injuries resulting in a PTA exceeding 1 hour but less than 1 week. Individual psychological testing was carried out as soon as the child recovered from PTA, and then again 4 months, 1 year, and 2¼ years after the injury. A shortened version of the Wechsler Intelligence Scale for Children (WISC), the Neale Analysis of Reading Ability and a battery of tests of specific cognitive functions were employed. The mild head injury group had a mean level of cognitive functioning below the control group, but the lack of any recovery during the follow-up period indicated that the intellectual impairment was not a consequence of the injury. In the severe head injury group, the presence of cognitive recovery and a ‘dose—response’ relationship with the degree of brain injury showed that the intellectual deficits were caused by brain damage. Some degree of cognitive impairment was common following head injuries giving rise to a PTA of at least 2 weeks. Conversely no cognitive sequelae, transient or persistent, could be detected when the PTA was less than 24 hours. The results were less consistent in the 1-day to 2-week PTA range, but the evidence suggested that a broadly defined threshold for impairment operated at about that level of severity of injury. Timed measures of visuo-spatial and visuo-motor skills tended to show more impairment than verbal skills but otherwise there was no suggestion of a specific pattern of cognitive deficit. Recovery was most rapid in the early months after injury, but substantial recovery continued for 1 year with some improvement continuing in the second year in some children, especially those with the most severe injuries. Age, sex and social class showed no significant effects on the course of recovery.

No abstract

BackgroundPretreatment with 17β-estradiol (E2) is profoundly neuroprotective in young animals subjected to focal and global ischemia. However, whether E2 retains its neuroprotective efficacy in aging animals, especially when administered after brain insult, is largely unknown.Methodology/Principal FindingsWe examined the neuroprotective effects of E2 and two agonists that bind to non-classical estrogen receptors, G1 and STX, when administered after ischemia in middle-aged rats after prolonged ovarian hormone withdrawal. Eight weeks after ovariectomy, middle-aged female rats underwent 10 minutes of global ischemia by four vessel occlusion. Immediately after reperfusion, animals received a single infusion of either E2 (2.25 µg), G1 (50 µg) or STX (50 µg) into the lateral ventricle (ICV) or a single systemic injection of E2 (100 µg/kg). Surviving pyramidal neurons in the hippocampal CA1 were quantified 1 week later. E2 and both agonists that target non-classical estrogen receptors (G1 and STX) administered ICV at the time of reperfusion provided significant levels of neuroprotection, with 55–60% of CA1 neurons surviving vs 15% survival in controls. A single systemic injection of a pharmacological dose of E2 also rescued approximately 50% of CA1 pyramidal neurons destined to die. To determine if E2 and G1 have similar mechanisms of action in hippocampal neurons, we compared the ability of E2 and G1 to modify CA1 pyramidal neuron responses to excitatory inputs from the Schaffer collaterals recorded in hippocampal slices derived from female rats not subjected to global ischemia. E2 and G1 (10 nM) significantly potentiated pyramidal neuron responses to excitatory inputs when applied to hippocampal slices.Conclusions/SignificanceThese findings suggest (1) that middle-aged female rats retain their responsiveness to E2 even after a long period of hormone withdrawal, (2) that non-classical estrogen receptors may mediate the neuroprotective actions of E2 when given after ischemia, and (3) that the neuroprotective efficacy of estrogens may be related to their modulation of synaptic activity in hippocampal slices.

Polycystic ovarian syndrome (PCOS) is a highly pre valent hormonal and metabolic disorder among repro ductive aged women worldwide. Women with PCOS have widely varying phenotypes and seek medical care for differing reasons. In addition to concern for men strual cycle function, ovulation, hirsutism and acne, many PCOS women have abnormal glucose metabolism. While diabetes mellitus and impaired glucose tolerance are easily diagnosed, the diagnosis of and concern for insulin resistance as a precursor disorder is under appreciated. Insulin resistance may be the first im portant marker of metabolic disease in PCOS women at risk for metabolic syndrome and coronary artery di sease.

The effects of pentagastrin, a synthetic analogue of the cholecystokinin tetrapeptide (CCK4), were studied in 15 patients with panic disorder and 15 healthy controls. Three different intravenous dosages of pentagastrin (0.1, 0.3 and 0.6 microgram/kg) and saline were investigated. Subjects were randomly allocated to two of the four treatment groups and tested on two separate occasions, 1 week apart, using an unbalanced double-blind incomplete block design. The mean panic rate with pentagastrin was 55% (12/22) for patients and 5% (1/22) for controls. None of the subjects panicked with saline. The frequency of panic attacks between the three pentagastrin doses in patients was not different. One control subject had a panic-like attack at the highest dose of pentagastrin. These findings concur with previous studies on the panicogenic effect of CCK4 and pentagastrin and suggest a greater sensitivity for CCK receptor agonists in patients suffering from panic disorder than in healthy controls.