Risk of early recurrent stroke in symptomatic carotid stenosis after best medical therapy and before endarterectomy.

BACKGROUND: The early recurrence of neurological symptoms (NR) after urgent aggressive best medical therapy (BMT) in symptomatic carotid stenosis is not well documented. AIMS: To investigate the risk of ipsilateral NR after urgent aggressive BMT in patients with symptomatic (50-99%) carotid stenosis up to carotid endarterectomy (CEA), with emphasis on the first 14 days after index-event. METHODS: Prospective population based study, covering a period of 4½ years. NR rate was determined after initiation of urgent aggressive BMT and until CEA and compared to NR up to 90 days prior to index-event. Urgent BMT consisted of loading dose aspirin and clopidogrel thereafter therapy with aspirin and clopidogrel together with a statin. RESULTS: Of 8200 symptomatic patients (ischemic stroke, transient ischemic attack and ocular events), 250 (3%) patients underwent CEA, 47% within 14 days of the index-event and 99% within 14 days of surgical referral. The overall NR from index-event to CEA in symptomatic patients was significantly lower 1.6% (95% CI 0.5-4%) after BMT when compared with NR in the 90 days prior to referral to a stroke clinic 25% (95% CI 20-30%, p < 0.00001). Peri-operative bleeding 5% (95% CI 3-8%) was comparable with other studies. CONCLUSION: Urgent aggressive BMT after index-event is associated with a significant reduction in the risk of early NR in CEA candidates. The early risk of recurrent stroke in patients with symptomatic significant carotid stenosis is dramatically reduced after urgent aggressive BMT in specialised stroke clinics.

Corrigendum to "Combination therapy with interferon and JAK1-2 inhibitor is feasible. Proof of concept with rapid reduction in JAK2V617F-allele burden in Polycythemia Vera" [Leuk. Res. Rep. 3 (2) (2014) 73-75].

[This corrects the article DOI: 10.1016/j.lrr.2014.05.003.].

Combination therapy with interferon and JAK1-2 inhibitor is feasible: Proof of concept with rapid reduction in JAK2V617F-allele burden in polycythemia vera.

We report a 55 year old woman with post-ET PV for 12 years, who experienced resolution of severe constitutional symptoms within 3 days, a marked reduction in splenomegaly and a rapid decline in the JAK2V617F allele burden during combination therapy with interferon-alpha2a and ruxolitinib. Within 4 weeks the patient achieved complete hematological remission with normalization of peripheral blood counts and within 10 months the JAK2V617F-allele burden was reduced from 90% to 28%. Such a rapid decline in the JAK2V617F allele burden is highly unusual in PV-patients during low-dose IFN-alpha2 monotherapy and this finding warrants a prospective study with combination therapy.

Tingling/numbness in the hands of computer users: neurophysiological findings from the NUDATA study.

OBJECTIVES: To investigate whether tingling/numbness of the hands and fingers among computer users is associated with elevated vibration threshold as a sign of early nerve compression. METHODS: Within the Danish NUDATA study, vibratory sensory testing with monitoring of the digital vibration threshold at seven frequencies on the second and fifth fingers of both hands was performed on 20 cases with unilateral tingling/numbness in the hands and fingers, and 20 gender- and age-matched controls. Both cases and controls were identified from questionnaire information about tingling/numbness at least once a week or daily within the last 3 months. Participants with more than slight muscular pain or disorders of the neck and upper extremities, excessive alcohol consumption, previous injuries of the upper extremities, or concurrent medical diseases were excluded. The two groups had a similar amount of work with mouse, keyboard, and computer. RESULTS: Seven of the 20 cases (35%) had elevated vibration thresholds, compared with 3 of the 20 controls (15%); this difference was not statistically significant (chi2=2.13, P=0.14). Compared with controls, cases had increased perception threshold for all frequencies, but the difference was statistically significant for only 2 out of 14 measurements. Comparison between left and right hand threshold values within the case group did not show any significant difference at any frequency. CONCLUSIONS: The results indicate that tingling/numbness of the hands and fingers among computer users cannot be explained by nerve compression.

Diagnostic yield by testing small fiber function in patients examined for polyneuropathy.

We assessed the diagnostic yield of adding quantitative sensory testing to the standard work-up for polyneuropathy in unselected patients. All patients aged 18 to 70 years referred to our department for electrodiagnosis with a tentative diagnosis of polyneuropathy and symptoms complying with predefined criteria were included in the study. We performed near nerve conduction studies in 4 nerves and determined heat and cold detection thresholds on hand and foot with a Thermotest (Somedic AB, Sweden). In order to uncover CNS diseases, somatosensory-evoked potentials were recorded in patients with abnormal quantitative sensory testing and normal nerve conduction studies. A total of 198 patients completed the study and 149 were considered to have polyneuropathy. Twenty-five patients remained undiagnosed and in 24 patients, other diseases were responsible for the symptoms. Of the patients with either polyneuropathy or no other diagnosis, 76% (n = 174) had abnormal nerve conduction. Abnormal cold sensation, heat sensation or abnormality in at least 1 of these and normal nerve conduction were found in 14, 12 and 17 patients. Of the 174 patients, 86% (95% CI 80-90%) had an abnormality in at least 1 of the tests (i.e. abnormal nerve conduction and/or abnormal quantitative testing of temperature sensation). In conclusion, quantitative testing of temperature sensation improves the diagnostic yield in patients examined for chronic polyneuropathy.

Vibrotactilometry as a diagnostic tool in ulnar nerve entrapment at the elbow.

Vibrotactilometry with testing of the thresholds of the vibration sense at seven frequencies between 8-500 Hz in different intensities has been correlated with nerve conduction studies of the ulnar nerve to evaluate its diagnostic power in neuropathies at the elbow. Thirty-nine patients with entrapment symptoms were studied. Vibrotactilometry was abnormal in 33 patients (85%) and nerve conduction studies were abnormal in 19 (49%). The sensitivity of vibrotactilometry in relation to nerve conduction studies was 89%, and in relation to the patients' symptoms was 85%. We conclude that vibrotactilometry is a sensitive test that correlates well with the patients' symptoms, while nerve conduction studies are less sensitive (49%) in relation to the patients' symptoms. Vibrotactilometry in the frequency area of 8-500 Hz is recommended in the screening of ulnar nerve entrapment. Nerve conduction studies are recommended in clinically doubtful cases to localise the entrapment to the elbow region.

MR imaging of the wrist in carpal tunnel syndrome.

PURPOSE: To determine whether specific parameters measured on MR images correlated to electrophysiological changes in carpal tunnel syndrome (CTS). MATERIAL AND METHODS: Prospective clinical examinations were made of 20 patients with suspected CTS. We performed bilateral electrophysiological examinations of the median nerve and bilateral MR imaging of the wrists. RESULTS: The electrophysiological examination suggested median nerve entrapment in 18 wrists. These wrists were compared to the remaining 22 electrophysiologically normal wrists. In addition, we compared both wrists in 12 patients with unilateral symptoms of CTS without reference to the electrophysiological findings. We found no difference in specific MR parameters between the 2 groups. CONCLUSION: Neither symptoms nor electrophysiological findings in CTS were related to specific MR parameters.

Thrombolytic therapy in acute ischemic stroke. A Danish pilot study.

BACKGROUND AND PURPOSE: In a feasibility and safety study of thrombolytic therapy in acute ischemic stroke, we explored the usefulness of measurements of regional cerebral blood flow. METHODS: Twenty-three patients with acute ischemic stroke were treated with 100 mg recombinant tissue plasminogen activator infused intravenously over 1 hour. Thrombolytic therapy was initiated 78 to 355 minutes after onset of symptoms. RESULTS: Angiography 16 to 24 hours after treatment in 17 patients showed patient intracranial arteries in 12, partial occlusion of the middle cerebral artery in 3, and total occlusion of the middle cerebral artery in 2. rCBF with 99mTc-hexamethylpropyleneamine oxime intravenously was measured 5 minutes before and within 24 hours after thrombolytic therapy in 12 patients. 10 of the 12 patients showed brain tissue reperfusion and 2, with angiographically documented middle cerebral artery occlusion, showed no reperfusion, thus documenting a relationship between reperfusion measured by regional cerebral blood flow and angiographic patency (P = .015). Three patients died. Patients who were reperfused within 24 hours (documented by repeated regional cerebral blood flow measurements) showed greater clinical improvement on the Scandinavian Stroke Scale the sooner their thrombolytic therapy was started and the more severe their neurological deficits. CONCLUSIONS: Acute cerebral ischemia can be documented by rCBF measurements without delay of thrombolytic therapy, and repeated rCBF measurements can reveal whether cerebral reperfusion has occurred. In our study, early reperfusion was associated with clinical improvement.

Alteplase therapy in acute ischemic stroke: a Danish pilot study.OFF.

In the period from October 1990 to December 1991, 23 patients with acute ischemic stroke were treated with recombinant tissue plasminogen activator (rt-PA) at a median of 205 min (range 78-355 min) after symptom onset. In this open pilot study rt-PA was given intravenously after an acute CT scan had not shown acute changes. In 12 patients regional cerebral blood flow was measured intravenously using 99mTc-HMPAO before and within 24 h after thrombolytic therapy. Reperfusion of the ischemic area was obtained in 10 patients. In these patients clinical improvement was greater the shorter the delay from symptom onset to initiation of treatment. Three of the 23 patients died, one of a parenchymatous hematoma, one of a large middle cerebral artery infarct, and one of acute myocardial infarction.

Sjögren's syndrome in patients with multiple sclerosis.

Twenty female patients with clinically multiple sclerosis were evaluated with regard to a possible underlying Sjögren syndrome. Two patients (10%) demonstrated a clinical Sjögren syndrome which does not differ significantly from the prevalence in an unselected population. Dry eye-symptoms occurred among MS-patients and should be subjected to relevant diagnostic procedures.

Trial of intravenous lidocaine on painful neuropathy in cancer patients.

In 10 cancer patients with cutaneous allodynia, intravenous lidocaine (5 mg/kg body weight) or 0.9% NaCl was given in a double blind, cross-over study to determine the analgesic effect. One patient had complete and one had partial pain relief with lidocaine infusion, whereas three patients experienced partial pain relief with placebo. Neither lidocaine nor placebo reduced pain intensity or consumption of analgesics significantly during the study period. Intravenous infusion of lidocaine cannot be recommended as routine pain treatment in cancer patients with cutaneous allodynia or pain, but further studies are needed to test the effect of lidocaine on different peripheral stimuli.

The antineoplastic effect of methylprednisolone pulse therapy in two patients with glucocorticoid receptor-positive glioblastoma multiforme.

Glucocorticoids in high concentrations inhibit in vitro the growth rate of glioblastoma multiforme. This presupposes the presence of glucocorticoid receptors in the cytoplasma. Glucocorticoid receptor positive patients with histological glioblastoma multiforme were postoperatively treated with high dose methylprednisolone pulse therapy during which CT-scanning initially demonstrated tumor regression. One patient's tumor size was unchanged after 24 weeks, whereas in the other patient, the tumor size after decreasing for 1 month began increasing again. The survival rate, at the present 15 and 10 months, without irradiation therapy and the decreasing glucocorticoid receptor concentrations at reoperations indicate an antineoplastic effect by continuous high-dose glucocorticoid pulse therapy.

Glucocorticoid receptors in glioblastoma multiforme: a new approach to antineoplastic glucocorticoid therapy.

Glucocorticoid receptors were measured in tissue samples from 12 patients with glioblastoma multiforme. The receptor was found in all patients. The concentration of glucocorticoid receptor was found to be high in the periphery of the tumour, low in the surrounding brain tissue and low in the central part of the tumour in 6 of the patients. The possible role of the glucocorticoid receptor distribution in relation to growth regulation is discussed. A decreasing receptor concentration found at reoperation in two patients indicates a possible antineoplastic effect of high dose methylprednisolone pulse therapy on glucocorticoid receptor positive glioblastomas.

Kinetics of insulin disappearance from plasma in cortisone-treated normal subjects.

The effect of glucocorticoid excess on insulin disappearance from plasma was examined in eight normal men during cortisone treatment (50 mg orally twice daily for 4 d) and in the absence of any medication (control) in random order. Constant infusion of insulin (1-5 mU/kg/min) was used to achieve different levels of steady state plasma insulin concentrations; normoglycaemia was preserved by a glucose clamp technique. The experimentally determined data were compared using a previously validated model of saturation kinetics. The amount of glucose required to maintain normoglycaemia during the insulin infusions was significantly less in the cortisone study than in the control study, while the parameter estimates for the kinetics of insulin disappearance from plasma were unaffected by cortisone. Thus, insulin action and insulin kinetics in the steady state are dissociated in normal subjects rendered insulin resistant by short-term cortisone treatment.

Kinetic models for insulin disappearance from plasma in type I diabetic patients.

We have tested whether our previous finding in normal subjects that the disappearance of insulin from plasma obeys saturation kinetics alone also applies to type I diabetic patients. In six long-term diabetic patients steady state plasma insulin concentrations resulting from constant insulin infusion at different rates were compared with the predictions of three models for the kinetics of insulin in plasma. The models allowed the existence of non-saturable (first order equation) or saturable (Michaëlis-Menten equation) mechanisms, or both. The minimal acceptable model included saturation kinetics alone in four subjects and first order kinetics alone in two subjects. The clearance of insulin in diabetic patients, calculated from the best fitting model, was 18.0 (median, range 10.0-23.7) ml X kg-1 X min.-1 versus 25.0 (18.6-47.1) ml X kg-1 X min.-1 in six normal subjects (2p = 0.008). Insulin thus disappears from plasma at a lower rate in diabetic patients than in normal subjects at physiological plasma concentrations.

Epidemiology and treatment of diabetic ketoacidosis in a community population.

We evaluated the epidemiology of diabetic ketoacidosis in the period 1960-1979. In Frederiksborg County, Denmark, the incidence of ketoacidosis at the county hospital increased from 60 per 100,000 in the period 1943-1963 to 120 per 100,000 in the period 1960-1979. In the investigation period we found an increasing incidence confined to urban areas. Precipitating factors were not somatic in 53% of the cases. Patients in the lowest social class (V) were in a higher risk group, experiencing ketoacidosis more often and having a higher frequency of severe acidosis. Forty-nine percent of the patients have had a diabetes duration of more than 5 yr. The lethality rate decreased from the period 1943-1963 and was 4.7% in the investigation period 1960-1979.

Therapeutic effect of tamoxifen versus tamoxifen combined with medroxyprogesterone acetate in advanced breast cancer in postmenopausal women.

Postmenopausal patients, those less than 68 years of age resistant to chemotherapy and those greater than 68 years of age with or without resistance to chemotherapy, entered this trial. Among 101 eligible patients, 46 were randomized to treatment with tamoxifen at a dose of 10 mg 3 times daily and 55 were randomized to treatment with tamoxifen at a dose of 10 mg 3 times daily plus medroxyprogesterone acetate at a dose of 100 mg once daily. Remission (partial plus complete) was obtained in 20 patients (45%) with tamoxifen compared to 14 patients (26%) with tamoxifen plus medroxyprogesterone acetate; however, this difference is not significantly different. The median duration of remission was also not significantly different between the two treatments: 10 months for the single drug compared with 9 months for the combined treatment. Response rates correlated with the presence of estrogen receptor, with no differences between the two treatment groups. Side effects occurred in 12 patients and in only one patient did they cause discontinuation of treatment. In conclusion, these results and theoretic considerations indicate that combined treatment with tamoxifen and medroxyprogesterone acetate is not better than treatment with tamoxifen alone.