Prognosis after cardiac arrest based on age and duration of coma.

In an attempt to determine the relation between duration of coma and neurologic recovery following cardiac resuscitation 163 survivors of cardiac arrest from Winnipeg, Manitoba and Aarhus, Denmark were studied. The age of the patients did not influence the outcome. Of the 153 patients who had awakened from the coma within 24 hours, only 11 suffered brain damage, compared with all of the 10 patients who wakened after 24 hours. The three who wakened after 72 hours had severe brain damage and required permanent care in an institution. It was concluded that recovery of communicative brain function is unlikely if coma persists longer than 72 hours after cardiac arrest and that full recovery cannot be expected after 24 hours of coma.     

Quantitation of the rate of spontaneous generation and carcinogen-induced frequency of anchorage-independent variants of rat tracheal epithelial cells in culture

The rate of spontaneous generation and the frequency of carcinogen-induced anchorage-independent variants of preneoplastic rat tracheal epithelial (RTE) cells in culture were quantitated. Anchorage-independent variants of different RTE cell lines arose spontaneously by a stochastic process at rates of 0.5 X 10(-4) to 5.4 X 10(-4) variants/cell/generation, as determined by fluctuation analyses. These variants were also induced by the mutagen N-methyl-N'-nitro-N-nitrosoguanidine with a frequency of approximately 10(-3) variants/surviving cell. The rates of spontaneous change and the frequencies of induction are the first reported for epithelial cells and are similar to some, although not all, rates and frequencies of change to anchorage independence for fibroblast-like cells in culture. In addition, these rates and frequencies are similar to those for mutations at some known gene loci. The induced frequency of this late change in neoplastic progression is, however, considerably lower than the frequency of induction of the initial, preneoplastic changes in RTE cells in culture (approximately 3 X 10(-2)/surviving cell). These quantitative determinations are useful in defining the mechanisms of late changes occurring during the progression of RTE cells to the neoplastic state.     

Prevalence of HTLV-I in arctic regions

Sera of native inhabitants of Arctic regions were assayed for antibodies to HTLV-I by the ELISA technique followed by competition experiments to confirm antibody specificity. Residents of 7 widely separated Alaskan villages exhibited prevalence rates of 0 to 12% for HTLV-I antibodies. Less than 1 % of Greenland Eskimos were HTLV-I antibody-positive. Residents of 3 northern Swedish regions ranged in HTLV-I antibody prevalence from 0 to 5%. Sera of healthy native inhabitants of Alaska and northern Sweden were similarly assayed for antibodies to HTLV-II. No additional sera were shown to be positive for HTLV-II antibodies. While some of the HTLV-I antibody-positive sera exhibited cross-reactivity with HTLV-II antigens, competition experiments using disrupted HTLV-II or purified HTLV-I p24 as test antigens indicated that the primary antibody response in all cases tested was elicited by HTLV-I. Our results show that HTLV-I distribution is not restricted to endemic areas in warm, humid climates, but extends to Arctic regions. Within these regions, HTLV-I exhibits the same restricted distribution seen in other areas where virus infection is prevalent. The Arctic does not seem to be a reservoir for HTLV-II infection. The origin of HTLV-I in Arctic areas is not known. One may speculate that foreign visitors introduced the virus into Aleut and Lapp populations, and that it has been maintained there and restricted in its distribution as a result of close familial relationships.     

Long-term effect of intravenous thrombolytic therapy in acute stroke: responder analysis versus uniform analysis of excellent outcome

BACKGROUND: Knowledge regarding functional improvement over time and long-term outcome after intravenous thrombolysis in acute ischaemic stroke is limited. The aim of this study was to compare a uniform assessment of outcome with an assessment taking the baseline stroke severity into account (responder analysis). METHODS: Fifty-seven patients were assessed with the modified Rankin Scale at 3, 6 and 12 months and a comparison was made between a uniform assessment and a responder analysis of excellent outcome. RESULTS: Between 3 and 12 months, 74% of the patients had a stable functional outcome and 22% improved. Excellent outcome at 12 months was similar in the uniform analysis (37%) and the responder analysis (35%). The individual patients having an excellent outcome differed, however, using the two methods. Using a responder analysis the number of patients with excellent outcome decreased in mild stroke patients by 40%, but increased in severe stroke patients by 43%. CONCLUSIONS: Short-term outcome is sustained at 12 months, but major improvement does not occur between 3 and 12 months. A responder analysis of long-term excellent outcome provided a balanced measure of outcome reflecting the drug-related potential of improvement in all stroke severity subgroups, whereas a uniform analysis provided a measure of outcome mainly in mild stroke patients. These results suggest that a responder analysis should be considered for the assessment of outcome after treatment for acute stroke.     

Effect of oral contraceptives on the anticoagulant activity of protein S in plasma

We determined anticoagulant parameters that depend on protein S function in plasma, i.e. the APC-independent anticoagulant activity of protein S (expressed as pSR) and APC resistance determined with thrombin generation-based tests (expressed as APCsr) as well as plasma levels of total and free protein S and prothrombin in men, women not using oral contraceptives (OC), and in women using second or third generation OC. Thrombin generation in the APC resistance assays was initiated either with factor Xa (Xa-APCsr) or tissue factor (TF-APCsr). The APC-independent anticoagulant activity of protein S was highest in men (pSR=1.69) and gradually decreased from women not using OC (pSR=1.49) via women using second generation (pSR=1.35) to women using third generation OC (pSR=1.27). The pSR correlated inversely with nAPCsr determined with the tissue factor-based APC resistance test (TF-APCsr) but not with nAPCsr determined with the factor Xa-based assay (Xa-APCsr). Multiple linear regression analysis in which sex, OC use, and protein S and prothrombin levels were included as independent variables and the pSR, TF-APCsr or Xa-APCsr as dependent variables indicated that plasma protein S levels poorly predict the pSR and the TF-APCsr, but are the main determinant of the Xa-APCsr. This indicates that OC use alters the expression of protein S activity. This phenomenon can be caused by differences in modulation of the activity of protein S by other plasma proteins that change during OC use or by OC-induced changes in the protein S molecule that impair its anticoagulant activity. Functional impairment of protein S as a result of hormonal influence may, at least in part, contribute to the thrombotic risk of OC users.     

Do all young ischemic stroke patients need long-term secondary preventive medication?

After a mean of 6 years, the frequencies of later vascular events (recurrent ischemic stroke or myocardial infarction) in 232 young ischemic stroke patients (younger than 50 years) with none to five traditional risk factors were 2.1%, 6%, 19%, 26%, 30%, and 67% (p < 0.001). Long-term secondary preventive medication may not be indicated in young ischemic stroke patients with no risk factor.     

Do indomethacin and propofol cause cerebral ischemic damage? Diffusion-weighted magnetic resonance imaging in patients undergoing craniotomy for brain tumors

BACKGROUND: Diffusion-weighted magnetic resonance imaging was used to determine whether indomethacin and propofol induce cerebral ischemic damage in patients undergoing craniotomy for cerebral tumors. As a secondary aim, the authors investigated whether low jugular bulb oxygen saturation values were associated with brain parenchymal damage as evaluated by diffusion-weighted imaging. METHODS: Nine patients subjected to craniotomy for supratentorial brain tumors in propofol-fentanyl anesthesia were studied. Magnetic resonance imaging including diffusion- and perfusion-weighted and structural sequences were performed (1) on the day before surgery, (2) before and (3) 20 min after administration of indomethacin (bolus of 0.2 mg/kg followed by infusion of 0.2 mg.kg.h) in the propofol-fentanyl-anesthetized patient, and (4) 2 days after surgery. Apparent diffusion coefficient maps were calculated. Jugular bulb oxygen saturation, arteriovenous oxygen difference, mean arterial blood pressure, and arterial oxygen and carbon dioxide tensions were measured simultaneously with the magnetic resonance examinations performed during anesthesia. RESULTS: No ischemic lesions were detected in the diffusion-weighted or apparent diffusion coefficient images. A nonsignificant decrease in jugular bulb oxygen saturation from 51% (range, 40-61%) to 43% (range, 37-63%) and increase in arteriovenous oxygen difference from 4.4 mm (range, 2.7-4.6 mm) to 4.7 mm (range, 2.9-5.2 mm) was observed after indomethacin administration. CONCLUSION: Administration of indomethacin during propofol anesthesia is not associated with evidence of ischemic damage in patients with brain tumors, as evaluated by diffusion-weighted imaging.     

Prediction of postoperative pain by preoperative nociceptive responses to heat stimulation

BACKGROUND: Despite major advances in the understanding of the neurobiologic mechanisms of pain, the wide variation in acute pain experience has not been well explained. Therefore, the authors investigated the potential of a preoperatively induced heat injury to predict subsequent postoperative pain ratings in patients undergoing knee surgery. METHODS: Twenty patients were studied. The burn injury was induced 6 days before surgery with a contact thermode (12.5 cm2, 47 degrees C for 7 min). The sensory testing, before and 1 h after the injury, included pain score during induction of the burn, secondary hyperalgesia area, thermal and mechanical pain perception, and pain thresholds. Postoperative analgesia consisted of ibuprofen and acetaminophen. Pain ratings (visual analog scale) at rest and during limb movement were followed for 10 days after surgery. RESULTS: The burn injury was associated with development of significant hyperalgesia. There was a significant correlation between preoperative pain ratings during the burn injury and early (0-2 days, area under the curve) and late (3-10 days, area under the curve) postoperative dynamic pain ratings during limb movement. CONCLUSION: The results of this study suggest that the pain response to a preoperative heat injury may be useful in research in predicting the intensity of postoperative pain. These findings may have important implications to identify patients at risk for development of chronic pain and to stratify individuals for investigations of new analgesics.     

Strength training increases insulin-mediated glucose uptake, GLUT4 content, and insulin signaling in skeletal muscle in patients with type 2 diabetes

Strength training represents an alternative to endurance training for patients with type 2 diabetes. Little is known about the effect on insulin action and key proteins in skeletal muscle, and the necessary volume of strength training is unknown. A total of 10 type 2 diabetic subjects and 7 healthy men (control subjects) strength-trained one leg three times per week for 6 weeks while the other leg remained untrained. Each session lasted no more than 30 min. After strength training, muscle biopsies were obtained, and an isoglycemic-hyperinsulinemic clamp combined with arterio-femoral venous catheterization of both legs was carried out. In general, qualitatively similar responses were obtained in both groups. During the clamp, leg blood flow was higher (P < 0.05) in trained versus untrained legs, but despite this, arterio-venous extraction glucose did not decrease in trained legs. Thus, leg glucose clearance was increased in trained legs (P < 0.05) and more than explained by increases in muscle mass. Strength training increased protein content of GLUT4, insulin receptor, protein kinase B-alpha/beta, glycogen synthase (GS), and GS total activity. In conclusion, we found that strength training for 30 min three times per week increases insulin action in skeletal muscle in both groups. The adaptation is attributable to local contraction-mediated mechanisms involving key proteins in the insulin signaling cascade.     

Craniotomy for supratentorial brain tumors: risk factors for brain swelling after opening the dura mater

OBJECT: Cerebral swelling often occurs during craniotomy for cerebral tumors. The primary aim in this study was to determine risk factors (intracranial pressure [ICP], patient characteristics, histopathological features, neuroimaging characteristics, anesthetic regimen, and perioperative physiological data) predictive of brain swelling through the dural opening. As a secondary aim the authors attempted to define subdural ICP thresholds associated with brain swelling. METHODS: The study population consisted of 692 patients (mean age 50+/-15 years) scheduled for elective craniotomy for supratentorial brain tumors. Brain swelling through the dural opening was estimated according to a four-point scale. The patients were dichotomized as those without cerebral swelling (that is, brain below the dura mater [59 patients] or brain at the level of the dura mater [386 patients]) and those with cerebral swelling (that is, moderate brain swelling [205 patients] or pronounced brain swelling [42 patients]). Logistic regression analysis was used to identify subdural ICP (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.72-2.1, p < 0.0001), midline shift (OR 1.06, 95% CI 1.02-1.11, p = 0.008), a diagnosis of glioblastoma multiforme (OR 2.1, 95% CI 1.01-4.3, p = 0.047), and metastasis (OR 2.9, 95% CI 1.3-6.9, p = 0.01) as independent risk factors of intraoperative brain swelling. Thresholds for ICP associated with brain swelling were defined as follows: at an ICP less than 5 mm Hg, brain swelling rarely occurred (5% probability); at an ICP greater than 13 mm Hg, brain swelling occurred with 95% probability; and at an ICP greater than 26 mm Hg, severe brain swelling occurred with 95% probability. CONCLUSIONS: Subdural ICP is the strongest predictor of intraoperative brain swelling. It is possible to define thresholds of cerebral swelling and the authors recommend subdural ICP measurement as a tool to initiate preventive measures to reduce ICP before opening the dura mater.