Quality of life of stroke survivors

Adaptation to stroke requires complex, long-term change in stroke survivors' lives. This study aimed at identifying those factors that influence quality of life (QOL) of geriatric stroke survivors 1–3 years post-discharge. The objectives were: to describe the overall quality of life of stroke survivors; to examine the relationships between sociodemographic variables, neurological variables, functional status, social support, perceived health status, depression, and overall QOL; and to determine the best predictors of QOL. Data were collected on 50 stroke survivors using a cross-sectional design and standardized questionnaires, including the Quality of Life Index, the Functional Independence Measure, the Social Support Inventory for Stroke Survivors and the Centre for Epidemiologic Studies Depression Scale. The overall quality of life of the study participants was low. The most important predictors of QOL were depression, marital status, quality of social support, and functional status. Depression was the strongest predictor of QOL. By employing a multi-dimensional perspective, this study confirmed that adaptation to stroke involves much more than physical function. Thus, rehabilitation programs for this group would be more effective if they are based upon a holistic approach.     

Management of acute submacular hemorrhage using recombinant tissue plasminogen activator and gas

· Purpose: To assess the effects of intravitreal injection of recombinant tissue plasminogen activator (rTPA) and gas on submacular hemorrhage in age-related macular degeneration (ARMD). · Methods: Eleven consecutive patients (11 eyes) with subretinal hemorrhage due to ARMD involving the fovea with elevation of the neurosensory retina were included in this study. Subretinal hemorrhage occured 12 h to 14 days before onset of therapy. Injection of rTPA through the pars plana in a dose of 50 or 100 μg was performed. Gas instillation (0.2–0.4 ml) followed rTPA injection, either immediately after injection (7 patients) or during the following day (4 patients). · Results: After intravitreal injection of rTPA, subretinal clots were totally or partially liquefied when treatment started up to 3 days after onset of bleeding. In all patients treated with 100 μg rTPA a large exudative retinal detachment of the inferior retina resulted, which reabsorbed spontaneously within 2 weeks. After reattachment of the exudative retinal detachment hyperpigmentation of the retinal pigment epithelium was noted. Temporary opacification of the vitreous was observed between the 2nd and 7th postoperative day in 5 eyes (45.5%). Postoperative visual acuity increased in 5 patients (45.5%). · Conclusion: Intravitreal application of rTPA followed by gas injection is a sufficient and convenient technique for effective removal of freshly formed submacular hemorrhage. Removal is mediated through combined enzymatic (rTPA) and mechanical (gas) effects. This technique offers a quick recovery of vision in eyes with less severe ARMD. Received: 5 January 1998 Revised version received: 25 March 1998 Accepted: 23 June 1998     

Fluorescent pseudo-peptide linear vasopressin antagonists: design, synthesis, and applications

Fluoresceinyl and rhodamyl groups have been coupled by an amide link to side-chain amino groups at positions 1, 6, and 8 of pseudo-peptide linear vasopressin antagonists (Manning et al. Int. J. Pept. Protein Res. 1992, 40, 261-267) through different positions on the fluorophore, to give tetraethylrhodamyl-DTyr(Me)-Phe-Gln-Asn-Arg-Pro-Arg-Tyr-NH2 (2), 4-HOPh(CH2)2CO-DTyr(Me)-Phe-Gln-Asn-Lys(5-carboxyfl uoresceinyl)-Pro-A rg-NH2 (4), 4-HOPh(CH2)2CO-DTyr(Me)-Phe-Gln-Asn-Lys(5- or 6-carboxytetramethylrhodamyl)-Pro-Arg-NH2 (5, 6), 4-HOPh(CH2)2CO-DTyr(Me)-Phe-Gln-Asn-Arg-Pro-Lys(5- or 6- carboxyfluoresceinyl)-NH2 (8, 9), and 4-HOPh(CH2)2CO-DTyr(Me)-Phe-Gln-Asn-Arg-Pro-Lys(5- or 6- carboxytetramethylrhodamyl)-NH2 (10, 11). The closer to the C-terminus the fluorophore, the higher the affinities of the fluorescent derivatives for the human vasopressin V1a receptor transfected in CHO cells. The compound 10 has a Ki of 70 pM, as determined by competition experiments with [125I]-4-HOPhCH2CO-DTyr(Me)-Phe-Gln-Asn-Arg-Pro-Arg-NH2. It showed a good selectivity for human V1a receptor versus human OT (Ki = 1.2 nM), human vasopressin V1b (Ki approximately 27 nM), and human vasopressin V2 (Ki > 5000 nM) receptor subtypes. All fluorescent analogues were antagonists as shown by the inhibition of vasopressin induced inositol phosphate accumulation. These fluorescent ligands are efficient for labeling cells expressing the human V1a receptor subtype, as shown by flow cytofluorometric experiments or fluorescence microscopy. They are also appropriate tools for structural analysis of the vasopressin receptors by fluorescence.     

Rapid induction of behavioral and neurochemical tolerance to cocaethylene, a model compound for agonist therapy of cocaine dependence

Rationale: Tolerance to abused drugs may impact on patterns of abuse, and in the case of agonist therapies, may be beneficial in that it reduces the reward value of a given dose of abused drug. Cocaethylene, a psychoactive metabolite resulting from concurrent alcohol and cocaine consumption, was examined because of its use in human research studies of drug reward mechanisms, and its potential as a model compound for an agonist based therapy for cocaine dependence. Objective: Comparisons were made between cocaine and cocaethylene in the acute development of tolerance to the neurochemical and behavioral effects of cocaine. With chronic exposure, tolerance to the behavioral effects of cocaine was examined. Methods: In awake rats with a microdialysis probe in the nucleus accumbens and a jugular catheter, an IV bolus/3-h infusion of cocaine or cocaethylene and a subsequent cocaine challenge was administered while extracellular dopamine and locomotion were monitored. Chronic IV treatment with cocaine, cocaethylene, and a water control was accomplished for 7 days using osmotic minipumps attached to jugular catheters. Animals were then challenged with an IV bolus of cocaine. Results: With acute treatment, the IV bolus of cocaethylene at the beginning of the infusion period resulted in an initial behavioral activation equivalent to that caused by cocaine, after which there was a striking difference in that the cocaethylene group displayed a return to predrug levels of activity, while the cocaine group showed high levels of activity throughout the 3-h period. Both cocaethylene and cocaine resulted in an initial increase in the extracellular concentration of dopamine. However, after that initial increase, levels of dopamine dropped in the cocaethylene group while the cocaine group levels remained elevated. A 1-week infusion of cocaine or cocaethylene resulted in tolerance to the behavioral activating effects of a subsequent cocaine challenge. Conclusions: These results demonstrate a rapid induction of tolerance to the behavioral and neurochemical properties of cocaethylene, resulting in a diminished behavioral response to a cocaine challenge both acutely, and after 7 days. The relevance of these data for the use of cocaethylene as a model compound for an agonist approach to therapy for cocaine dependence is discussed. Received: 22 January 1999 / Final version: 16 April 1999     

Acute and chronic effects of nornicotine on locomotor activity in rats: altered response to nicotine

Rationale: Nicotine, a tobacco alkaloid, is known to be important in the acquisition and maintenance of tobacco smoking. Nornicotine, an active nicotine metabolite, stimulates nicotinic receptors and may produce psychomotor effects similar to nicotine. Objective: The present study determined the effects of acute and repeated administration of nornicotine on locomotor activity and compared its effects with those of nicotine. Methods: R(+)-Nornicotine (0.3–10 mg/kg), S(–)-nornicotine (0.3–10 mg/kg), S(–)-nicotine (0.1–1 mg/kg) or saline was administered s.c. to rats acutely or repeatedly (eight injections at 48-h intervals). Activity was recorded for 50 min immediately after each injection. Results: S(–)-Nicotine produced transient hypoactivity, followed by dose-related hyperactivity. Repeated S(–)-nicotine administration resulted in tolerance to the hypoactivity and sensitization to the hyperactivity. Subsequent testing following a saline injection revealed evidence of conditioned hyperactivity. Acute administration of 0.3 mg/kg or 1 mg/kg R(+)- or S(–)-nornicotine produced no effect. Transient hypoactivity was observed at 3 mg/kg and 10 mg/kg R(+)-nornicotine and at 10 mg/kg S(–)-nornicotine. However, rebound hyperactivity was not observed following acute administration of either nornicotine enantiomer, suggesting that nornicotine-induced psychomotor effects differ qualitatively from those of S(–)-nicotine. Repeated R(+)-nornicotine resulted in tolerance to the transient hypoactivity, however hyperactivity was not observed. Repeated S(–)-nornicotine resulted in tolerance to the hypoactivity and the appearance of hyperactivity. Repeated administration of either nornicotine enantiomer resulted in a dose-dependent alteration in response to a 1 mg/kg S(–)-nicotine challenge, suggesting some commonalities in the mechanism of action. Conclusion: Nornicotine likely contributes to the neuropharmacological effects of nicotine and tobacco use. Received: 11 January 1999 / Final version: 25 March 1999     

Matrix Metalloproteinase Inhibitors: Applications in Oncology

Matrix metalloproteinases (MMP) are a group of zinc dependentenzymes which include the interstitial collagenases, stromelysins,gelatinases and membrane-type metalloproteinases. They are involvedin the remodelling and turnover of the extracellular matrixproteins. They play a role in wound healing and the pathogenesis ofarthritis. In malignancies they play a role in tumor invasion,metastasis and angiogenesis. A number of synthetic matrixmetalloproteinase inhibitors (MMPIs) have been developed forclinical use. In preclinical tumor models they have shown promisingactivity in achievinginhibition of MMPs and reducing tumor growth and metastatic spread.Some have also shown additive or synergistic effects with cytotoxicagents. Phase I and II studies in human subjects have defined themain side effects of these agents as beingmusculoskeletal pains or arthralgias. As they are cytostatic agentsrather than cytotoxic in activity conventional measurements ofradiological response for assessment are not applicable in trials.Biological activity has been demonstrated in certain cancers by theeffects on levels of tumor markers as surrogate markers of tumorresponse and also by a fibrotic stromal reaction seen in tumortissue. Newer agents have been developed withselective inhibition of certain MMPs in an attempt to reduce theside effects. A number of phase III human clinical trialsevaluating MMPs are being carried out at present but onlyone has been formally reported so far. This study suggested thatmarimastat had no survival advantage when compared to chemotherapywith gemcitabine in advanced pancreatic carcinoma. Current trialsare assessing efficacy of MMPIs in maintenance of remission afterother modalities of therapy or in combination with cytotoxicagents. MMPs have also been demonstrated to play an important rolein the articular cartilage destruction seen in both rheumatoidarthritis and osteoarthritis. The use of MMPIs in both exvivoand in vivomodels have shown promising resultsand trials are in process to assess their potential role in thecontrol of articular destruction. The true therapeutic role ofMMPIs await the results of these randomized studies.     

Metabolic base production and mucosal vulnerability during acid inhibition in a mammalian stomachin vitro

Acid inhibition increases gastric mucosal susceptibility to damage by luminal acid. This might be due to reduced metabolic CO₂ and bicarbonate whereas, during normal acid, secretion cytoprotective CO₂/HCO₃- production parallels acid production. Metabolic activity and mucosal damage caused by luminal acid perfusion was determined in anin vitro mouse stomach, with and without acid inhibition, and at 0%, 1%, or 5% serosal CO₂ supply. Without acid inhibition there was no mucosal damage at any level of serosal CO₂/HCO₃- supply. Acid inhibition reduced metabolic CO₂ production by 29% (P<0.004) and resulted in microscopic damage to 55% of the mucosal area and perforation in four of five stomachs (P<0.05). Although, 1% CO₂ supply completely replaced the reduction in metabolic CO₂, it did not protect against mucosal damage. Overreplacement by 5% serosal CO₂/HCO₃- was required to prevent damage. There was no correlation between luminal CO₂/HCO₃- output and mucosal damage. The protection by endogenous or exogenous CO₂/HCO₃- appears to act intracellularly rather than by intragastric or intercellular neutralization.This study was supported by Swiss National Foundation grants 32-26369.89 and 32-33626.92. The morphometry equipment was supported by a grant from the Osterreichische Nationalbank.     

Update on Hyperlipidemia in the Elderly: Is This a Risk Factor for Heart Disease?

Results concerning the utility of lipid screening in the elderly are conflicting. Many studies have shown no association between total cholesterol measurements in the elderly and the development of coronary heart disease (CHD). Several recent investigations, with a few exceptions, have demonstrated that high-density lipoprotein-cholesterol (HDL-C) levels and the total/HDL-C ratio are, however, effective markers for CHD in older populations. Although the relative risk associated with lipid measurements tends to decline in older persons, the attributable risk for CHD associated with higher cholesterol and lower HDL-C tends to be greater in older persons because of a greater number of events in this population. Clinical trials with modern lipid-lowering agents have demonstrated efficacy and safety in middle-aged subjects with the newer medications, and it is time to consider a lipid altering clinical trial specifically targeted to persons over the age of 65 years to determine whether morbidity and mortality can be reduced.     

Automatic decomposition electromyography in idiopathic inflammatory myopathies

Automatic decomposition electromyography (ADEMG) is a commercially available software package with installed reference values that enables the objective measurement of motor unit action potentials (MUAPs). To assess the diagnostic yield of this package in idiopathic inflammatory myopathies (IIM) we performed biceps brachii ADEMG in 17 patients with polymyositis, dermatomyositis and inclusion body myositis. Results were compared with those in 12 controls, and with the results of conventional EMG of the biceps and other muscles. Decreased mean values for MUAP duration occurred significantly more frequently in IIM patients than in controls; other MUAP characteristics did not differ. In IIM patients, decreased mean amplitude and increased mean number of turns occurred significantly less frequently on ADEMG than did corresponding abnormalities on conventional biceps EMG. Decreased mean values for duration and amplitude, and increased mean values for number of turns were seen significantly less often on ADEMG than corresponding abnormalities on conventional EMG of four different, individually chosen muscles. Overall evaluation of ADEMG resulted in a diagnosis of possible myopathy in 1 and probable myopathy in 8 patients, whereas overall evaluation of conventional EMG led to a diagnosis suggestive of IIM in 13 patients. We conclude that, although measurement of mean MUAP duration might be valuable in IIM diagnosis, our results do not favour the use of biceps brachii ADEMG and the installed reference values for the diagnosis of IIM. We suggest modifications to improve ADEMG's applicability.     

Antihyperglycaemic effect of saccharin in diabetic ob/ob mice

1. The effect of chronic saccharin (benzosulphimide) consumption on glucose homeostasis was examined in normal lean +/+ mice and genetically obese hyperglycaemic insulin-resistant ob/ob mice.
2. Consumption of a 5% (w/v) sodium saccharin solution for 7 weeks prevented the development of hyperglycaemia, improved glucose tolerance (area under curve decreased by 51%), reduced the extent of hyperinsulinaemia (by 21%), and reduced excessive weight gain (by 18%) in ob/ob mice.
3. Consumption of 5% (w/v) sodium saccharin temporarily decreased hyperphagia at the beginning of treatment, decreased hepatic glycogen content (by 47%), increased abdominal muscle glycogen content (by 82%), but did not significantly alter the hypoglycaemic response to exogenous insulin in ob/ob mice.
4. Consumption of a 1% (w/v) sodium saccharin solution did not prevent the development of hyperglycaemia in ob/ob mice.
5. Normal lean +/+ mice consuming 5% (w/v) sodium saccharin solution showed a marginal decrease (by 8%) in glycaemia, and glucose tolerance was improved (area under curve decreased by 30%) without a significant change in the insulin response to glucose or the hypoglycaemic effect of exogenous insulin.
6. The results suggest that chronic consumption of saccharin can defer the development of hyperglycaemia and improve glucose homeostasis in insulin-resistant ob/ob mice through a mechanism that is independent of insulin.