The emerging role of induced hypothermia in the management of acute stroke.

Current treatment of acute stroke remains unsatisfactory. This review presents experimental and clinical data which suggest that mild induced hypothermia could be a potent and practicable neuroprotective treatment of acute ischaemic stroke and intracerebral haemorrhage. Hypothermia, if proven to be safe, effective and widely practicable in patients with acute stroke, could have an enormous positive impact on reducing the burden of stroke worldwide. Critical issues that will need to be considered in a well designed randomised controlled trial of induced hypothermia in acute stroke patients are discussed.     

Collateral sensitivity to nitrosoureas in multidrug-resistant cells selected with verapamil.

We have examined the effects of the nitrosoureas, streptozotocin (STZ) and 1,3-bis(chloroethyl)-1-nitrosourea (BCNU), on a human multiple myeloma cell line, RPMI 8226, and its drug-resistant variants. Cell lines selected for doxorubicin (DOX) resistance alone displayed a STZ and BCNU cytotoxicity profile similar to that of the parent cell line. In contrast, two of the drug-resistant variants selected with DOX plus verapamil, an agent which inhibits P-glycoprotein-mediated multidrug resistance, displayed a collateral sensitivity to STZ and BCNU. Verapamil was included in the selection protocol because it has been shown to inhibit the P-glycoprotein-mediated multidrug resistance phenotype and is now in clinical trials as a chemosensitizing agent. The collateral sensitivity to these nitrosoureas seen in the DOX plus verapamil-selected cell lines is due to the functional loss of a DNA repair molecule, O6-Methylguanine DNA methyltransferase (MGMT). The functional loss of MGMT is secondary to the loss of MGMT gene expression. The loss of MGMT gene expression is not due to loss or gross rearrangement of the MGMT-coding region. If this selection pressure applied in vitro reflects the in vivo situation, then new chemotherapeutic strategies may be devised to exploit this phenomenon. These cell lines will serve as useful models for delineating mechanisms which govern MGMT expression.     

GnRH receptor signalling to ERK: kinetics and compartmentalization.

Many hormones, neurotransmitters and growth factors influence their target cells by activation of mitogen-activated protein kinase cascades. The consequences of such activation reflect not only the magnitude, but also the kinetics and cellular compartmentalization of kinase activity. Gonadotropin-releasing hormone (GnRH) receptors are seven-transmembrane receptors that have undergone a period of rapidly accelerated molecular evolution in which the advent of type I mammalian GnRH receptors has been associated with the loss of the carboxyl-terminal tail, a structure present in all other seven-transmembrane receptors. Here, we review spatiotemporal aspects of extracellular-signal-regulated kinase activation by gonadotropin-releasing hormone receptors, emphasizing how the absence or presence of the carboxyl-terminal tail dictates the receptors' ability to engage and signal via arrestins.     

Coronary venous retroperfusion of arterial blood for the treatment of acute myocardial ischemia

Synchronized coronary venous retroperfusion of autologous arterial blood was offered to patients referred for medically refractory unstable angina or evolving myocardial infarction with contraindications to thrombolytic therapy. Primary endpoints of angina, ST segment deviation, and two-dimensional echocardiographic systolic wall motion were followed to determine the efficacy of retroperfusion in patients prior to and then during angioplasty, surgical intervention, or pharmacological management, as the clinical picture warranted. Over a 12 month period, 21 patients were referred and 15 received retroperfusion. All experienced full relief of angina (p = 0·008). ST segment deviations and systolic wall motion of ischemic zones were observed to improve (p = 0·06 ST changes; p = 0·0001 wall motion changes) with synchronized retrograde perfusion. During attempts to remove patients from retroperfusion, statistically significant (p < 0·01) reproducible changes in these same endpoints were documented. Retroperfusion appears to improve acute myocardial ischemia. This technique functions well in the intensive care unit environment with only fluoroscopy as technical imaging support.     

Lessons from the United Kingdom: fightback on workplace hazards, 1979-1992.

For the past 13 years there has been an aggressive anti-union government in the United Kingdom. Yet despite this fact, very real advances have been made in the area of working-class activity over the issue of workplace hazards. Trade unions, because of membership concern and activity, have been forced to keep this topic on their agenda. The European Community has been a big factor in these advances. This article describes some of the issues and elements of the fightback. In the 1990s, with the rediscovery of environmental issues, the hazards movement of the United Kingdom, and elsewhere, is here to stay and set to expand.     

Total shoulder replacement

It appears that total shoulder replacement can be performed with a high degree of patient satisfaction, with few complications, and with long-term results which certainly appear to rival the success of other arthroplasties. However, the technique is extremely demanding and requires an experienced shoulder surgeon, who must successfully resolve numerous intraoperative variables and problems, must be able to deal with factors which may affect the stability and strength of the implant, and must individualize the postoperative rehabilitation according to quality of bone and soft tissue, as well as the specific needs and desires of the patient. However, when performed technically satisfactorily with proper patient selection, with meticulous attention to the details of the soft tissue surrounding the implant, and with attention to the postoperative rehabilitation, the results have been impressive. Total shoulder replacement has successfully taken its place in the armamentarium of other total joint replacements which have dramatically altered the quality of life in the arthritic patient.     

The Adolescent Outcome of Hyperactive Children Diagnosed By Research Criteria—III. Mother–Child Interactions, Family Conflicts and Maternal Psychopathology

The present study reports the results of a prospective, 8-year follow-up study of 100 hyperactive and 60 normal children followed from childhood into adolescence. Ratings of child behavior problems and family conflicts as well as direct observations of mother-child interactions were taken in childhood and again at adolescent follow-up. At outcome, hyperactives continued to have more conduct and learning problems and to be more hyperactive, inattentive, and impulsive than controls. Hyperactives were also rated by their mothers as having more numerous and intense family conflicts than the normal controls, although the adolescents in both groups did not differ in their own ratings of these conflicts. Observations of mother-adolescent interactions at outcome found the hyperactive dyads displaying more negative and controlling behaviors and less positive and facilitating behaviors towards each other than in the normal dyads. These interaction patterns were significantly related to similar patterns in mother-child interactions observed 8 years earlier. Mothers of hyperactives also reported more personal psychological distress than normal mothers at outcome. Further analyses of subgroups of hyperactives at outcome, formed on the presence or absence of ADHD and oppositional defiant disorder (ODD), indicated that the presence of ODD accounted for most of the differences between hyperactives and normals on the interaction measures, ratings of home conflicts, and ratings of maternal psychological distress. Results suggest that the development and maintenance of ODD into adolescence in hyperactive children is strongly associated with aggression and negative parent-child interactions in childhood.