Effects of auditory stimuli on intracranial pressure and cerebral perfusion pressure in traumatic brain injury

In the kidney, ischaemia-reperfusion results in both hypoxic and oxidant cellular injury which is most marked in the tubules of cortex and outer medulla. These contrasting conditions may have opposite effects on the expression of enzymes that reduce or repair oxidant damage. To investigate this, the activities of CuZn and Mn superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST) were measured after 4 h and 3, 6, and 10 days of reperfusion following sham surgery or 45- or 90-min left renal artery occlusion. The right kidney served as internal control. Sham surgery had no effect on Mn SOD or GPx, but caused small (p < 0.05) reductions in CuZn SOD and GST activities. Forty-five minutes of ischaemia had no net effect on Mn SOD, increased GPx activity (maximum at 6 days, p < 0.01), and reduced CuZn SOD (nadir 3 days, p < 0.02) and GST (nadir 6 days, p < 0.02) activities. Ninety minutes of ischaemia again had no net effect on Mn SOD, prevented the induction of GPx, and further suppressed the activities of CuZn SOD and GST. The activity of the non-anti-oxidant enzyme lactate dehydrogenase was equal in left and right kidneys after 45 min of ischaemia, but different (p < 0.01) 10 days following 90-min injury, due to a combination of reduced activity in the ischaemic kidney and an increase of activity in the internal control. The immediate effect of ischaemia-reperfusion injury on the kidney is to reduce the activity of intracellular anti-oxidant enzymes in proportion to the severity of the ischaemic insult. Recovery or net induction of enzyme activity paralleled tubular regeneration. Protection resulting in acquired resistance to a second ischaemic event is unlikely to be due to induction of anti-oxidant enzymes if it occurs within 6 days.     

The psychosocial impact of skin disease. An overview

When the skin is disfigured by disease, it has an impact on the afflicted person. The intensity of the effect depends on many variables including the natural history of the disease, the characteristics of the individual patients and their life situation, as well as the attitudes and assumptions of the culture at large about the meaning of skin disease. Fantasies about skin disease, shared by patients and onlookers alike, relate to guilt, control of bodily boundaries, and perfectionist yearnings. Some issues involved in these fantasies include distortions about contagion, dirt, and sexuality. Ways of helping patients to manage the impact of their skin disease include an empathic doctor-patient alliance, education of patients and the community, and if indicated, referral for psychiatric consultation.     

HAH1 is a copper-binding protein with distinct amino acid residues mediating copper homeostasis and antioxidant defense

HAH1 is a 68-amino acid protein originally identified as a human homologue of Atx1p, a multi-copy suppressor of oxidative injury in sod1 delta yeast. Molecular modeling of HAH1 predicts a protein structure of two alpha-helices overlaying a four-stranded antiparallel beta-sheet with a potential metal binding site involving two conserved cysteine residues. Consistent with this model, in vitro studies with recombinant HAH1 directly demonstrated binding of Cu(I), and site-directed mutagenesis identified these cysteine residues as copper ligands. Expression of wild type and mutant HAH1 in atx1 delta yeast revealed the essential role of these cysteine residues in copper trafficking to the secretory compartment in vivo, as expression of a Cys-12/Cys-15 double mutant abrogated copper incorporation into the multicopper oxidase Fet3p. In contrast, mutation of the highly conserved lysine residues in the carboxyl terminus of HAH1 had no effect on copper trafficking to the secretory pathway but eliminated the antioxidant function of HAH1 in sod1 delta yeast. Taken together, these data support the concept of a unique copper coordination environment in HAH1 that permits this protein to function as an intracellular copper chaperone mediating distinct biological processes in eucaryotic cells.     

Treatment of compulsive behaviour in eating disorders with intermittent ketamine infusions

We have previously shown that eating disorders are a compulsive behaviour disease, characterized by frequent recall of anorexic thoughts. Evidence suggests that memory is a neocortical neuronal network, excitation of which involves the hippocampus, with recall occurring by re-excitement of the same specific network. Excitement of the hippocampus by glutamate-NMDA receptors, leading to long-term potentiation (LTP), can be blocked by ketamine. Continuous block of LTP prevents new memory formation but does not affect previous memories. Opioid antagonists prevent loss of consciousness with ketamine but do not prevent the block of LTP. We used infusions of 20 mg per hour ketamine for 10 h with 20 mg twice daily nalmefene as opioid antagonist to treat 15 patients with a long history of eating disorder, all of whom were chronic and resistant to several other forms of treatment. Nine (responders) showed prolonged remission when treated with two to nine ketamine infusions at intervals of 5 days to 3 weeks. Clinical response was associated with a significant decrease in Compulsion score: before ketamine, mean +/- SE was 44.0 +/- 2.5; after ketamine, 27.0 +/- 3.5 (t test, p = 0.0016). In six patients (non-responders) the score was: before ketamine, 42.8 +/- 3.7; after ketamine, 44.8 +/- 3.1. There was no significant response to at least five ketamine treatments, perhaps because the compulsive drive was re-established too soon after the infusion, or because the dose of opioid antagonist, nalmefene, was too low.     

Coping with indefinite and negative data in deductive databases: A survey

A problem with current database systems is the limitation placed on the type of data which may be represented and manipulated within such systems. In an attempt to broaden this to a wider class of data (i.e. rules as well as facts) and a more powerful set of manipulations, the concept of a deductive database was introduced. However, for the sake of efficiency the type of rule which is allowed in a deductive database is restricted in form. This paper surveys a number of attempts to move towards less restrictive forms of rules in deductive databases which allow indefinite and negative data to be handled.     

Arnold-Chiari malformation in a captive African lion cub

PURPOSE: Surgery and systemic chemotherapy offer modest benefit to patients with recurrent glioblastoma multiforme. These tumors are associated with rapid growth and progressive neurological deterioration. Radiosurgery offers a rational alternative treatment, delivering intensive local therapy. A pilot protocol to treat recurrent glioblastoma was developed using fractionated stereotactic radiosurgery with concurrent intravenous (i.v.) Taxol as a radiation sensitizer. METHODS AND MATERIALS: The treatment outcome was analyzed in 14 patients with recurrent glioblastoma treated with fractionated stereotactic radiosurgery and concurrent Taxol. Median tumor volume was 15.7 cc and patients received a mean radiation dose of 6.2 Gy at 90% isodose line, 4 times weekly. The median dose of Taxol was 120 mg/m2. RESULTS: The median survival was 14.2 months, 1-year survival was 50%. CONCLUSIONS: Survival for this small group of patients was similar to or better than historical controls or patients treated with single-fraction radiosurgery alone. This data should stimulate the investigation of both fractionated radiosurgery and the development of radiation sensitizers to further enhance treatment.     

Delorme operation for rectal prolapse

A consecutive series of 49 elderly patients of mean age 73 years with full-thickness rectal prolapse underwent the Delorme operation between 1986 and 1990. A standard technique was used, or supervised, by one surgeon. In this prospective series, 43 patients were reviewed clinically. The Delorme operation abolished rectal prolapse in 32 patients. Half of the 40 with faecal incontinence were rendered continent. Failure was related to previous anorectal surgery and/or psychiatric illness. Of the 11 patients in whom the first procedure failed, four were improved by a second Delorme operation. The Delorme operation is a suitable procedure for elderly and/or medically unfit patients with rectal prolapse. Good results have also been demonstrated for younger patients, suggesting that the operation may have wider application.     

In vitro expression of the diphtheria toxin A-chain gene under the control of human chorionic gonadotropin gene promoters as a means of directing toxicity to ovarian cancer cell lines

OBJECTIVE: Our goal was to determine whether toxicity of the diphtheria toxin A-chain gene regulated by the human chorionic gonadotropin promoter can be directed to malignant ovarian cell lines. STUDY DESIGN: Plasmids containing diphtheria toxin A-chain gene linked to the regulatory elements of the metalloergothioneine and human chorionic gonadotropin promoters were transfected into the cell lines. Expression of diphtheria toxin A-chain gene was determined by the inhibition of a cotransfected luciferase reporter gene. RESULTS: Cytotoxicity of the diphtheria toxin A-chain gene is shown in a dose-responsive manner. Transfection of a plasmid expressing the diphtheria toxin A-chain gene controlled by a constitutive promoter readily inhibits protein synthesis. Specific inhibition of luciferase protein synthesis occurs in ovarian cancer cells transfected with the diphtheria toxin A-chain gene under the control of the human chorionic gonadotropin promoters when compared with normal ovarian epithelial cells or fibroblasts. CONCLUSIONS: These data demonstrate the preferential expression of the diphtheria toxin A-chain gene, regulated by the human chorionic gonadotropin promoter, to ovarian cancer cell lines. This provides an avenue for targeting such cells for suicide, toxin, or cytokine genes.