Early microalbuminuria as a clinical marker for acute cerebral small vessel infarction.

BACKGROUND: Previous studies have shown the potential interactions between cerebrovascular diseases and microalbuminuria. However, the relationship between urine microalbumin and acute lacunar infarction caused by cerebral small vessel disease (CSVD) remains unknown. METHODS: The clinical data of 148 patients with acute lacunar infarction admitted to the Department of Neurology, Shengjing Hospital of China Medical University between April 2016 and April 2017 were analyzed. They were divided into either a CSVD group (n = 70) or a cerebral large vessel disease (CLVD) group (n = 78) according to their carotid artery B-mode ultrasonography and head magnetic resonance angiography (MRA) findings. The concentration of urinary microalbumin in both groups was determined. Statistic analysis was conducted using SAS 9.1 software (North Carolina state university, USA). A Logistic regression analysis was used to determine the independent risk factors for acute lacunar infarction caused by CSVD. RESULTS: The concentration of urine microalbumin in the CSVD group (23 ± 12 mg/L) was significantly lower than that in the CLVD group (29 ± 15 mg/L) (p < 0. 01). However, there was an increasing trend for the proportion of patients with urine microalbumin concentration 10- < 30 mg/L (34.3%) in the CSVD group compared with the CLVD group (19.2%). Logistic regression analysis showed that microalbuminuria (10- < 30 mg/L) was independently associated with acute lacunar infarction caused by CSVD (OR = 3.582; 95% CI 1.347～6.274; p < 0.01). CONCLUSIONS: These findings demonstrate that in patients with acute lacunar infarction, slightly increased microalbuminuria seems to be a potential clinical marker for CSVD. The presence of microalbuminuria early may help to differentiate CSVD from stroke subtypes.

Study on the effect of urinary kallidinogenase after thrombolytic treatment for acute cerebral infarction.

OBJECTIVE: To evaluate the safety and efficacy of urinary kallidinogenase for recombinant tissue-type plasminogen activator (rt-PA) intravenous thrombolytic treatment in patients with acute cerebral infarction. PATIENTS AND METHODS: All 200 patients with acute cerebral infarction were randomized 1:1 into an experimental group (100 cases) and a control group (100 cases). Patients in the control group were administrated rt-PA (0/9 mg/kg) while patients in the experimental group were given urinary kallidinogenase by intravenous drip (0.15 PNAU/d, for 7 days) after rt-PA intravenous thrombolytic treatment (0.9 mg/kg). The main evaluation index was NIHSS and BI. RESULTS: Compared to the control group, the NIHSS scores were significantly lower 7 and 90 days after thrombolytic therapy (t = 2.391, 2.714; p < 0.05). BI scores were obviously higher at 90 days after thrombolytic therapy in the experimental group (t = 2.675, p < 0.05). CONCLUSIONS: Urinary kallidinogenase may improve the treatment effect for rt-PA intravenous thrombolytic treatment in patients with acute cerebral infraction.

Serial urinary 11-dehydrothromboxane B2, aspirin dose, and vascular events in blacks after recent cerebral infarction.

BACKGROUND AND PURPOSE: Incomplete platelet inhibition by aspirin (aspirin resistance) may be a reason for stroke recurrence in some patients. 11-dehydrothromboxane B2 (11-DTB2) is a stable thromboxane A2 metabolite that reflects in vivo platelet activation. This pilot study was intended to evaluate the reproducibility of urinary 11-DTB2 over time and to look for evidence of aspirin resistance. METHODS: All subjects were screened for the African American Antiplatelet Stroke Prevention Study (AAASPS) 7 to 90 days after noncardioembolic cerebral infarction. Of 83 subjects with at least 1 urine sample, 52 were enrolled in AAASPS (randomized to blinded treatment with aspirin 650 mg/d or ticlopidine 500 mg/d), and 31 were enrolled in an open-label antiplatelet therapy cohort. Subjects were followed up for 2 years, with 11-DTB2 measurements scheduled at baseline and 6, 12, and 24 months. Vascular events were cerebral infarction, myocardial infarction, or vascular death. RESULTS: Despite considerable individual up or down fluctuations, the median 11-DTB2 change did not significantly differ from zero in any of the subgroups. However, in 6 subjects with a 4-fold decrease in aspirin dose from 1300 to 325 or 81 mg/d, the 11-DTB2 level increased from 611 to 1881 pg/mg creatinine (P=0.06). Vascular events occurred in 7 of 61 aspirin-treated subjects, and 11-DTB2 levels did not correlate with the events. CONCLUSIONS: Fluctuations in urinary 11-DTB2 after cerebral infarction in blacks do not correlate with changes in aspirin doses, except perhaps when the dose changes by a factor of 4 or more. A larger study is needed to look further for aspirin resistance.

Urinary excretion of aquaporin-2 and inappropriate secretion of vasopressin in hyponatremic patients after cerebral infarction.

Aquaporin-2, a water-channel protein, is known to increase water permeability due to vasopressin binding to V2 receptors at the renal collecting duct and is excreted into the urine. It is still unclear whether a hyponatremic state is caused by vasopressin-dependent aquaporin-2 in patients clinically diagnosed with the syndrome of inappropriate secretion of antidiuretic hormone. To determine this, we measured urinary aquaporin-2 and vasopressin by radioimmunoassay in normonatremic or hyponatremic patients after cerebral infarction and in healthy controls. In the normonatremia group, urinary aquaporin-2 and plasma AVP levels were higher than in controls. In the hyponatremia group, plasma AVP was relatively high despite low plasma osmolality in each patient. However, urinary aquaporin-2 in hyponatremia was significantly increased when compared with the other two groups. In conclusion, AQP-2 increment does not directly reflect non-osmotic AVP secretion in a hyponatremic state. This result indicates that the urinary excretion of AQP-2 is not only AVP-dependent in hyponatremic states.

Urinary 11-dehydro-thromboxane B2: a quantitative index of platelet activation in cerebral infarction.

Thromboxane A2 (TXA2) biosynthesis was studied in healthy subjects, patients with chronic cerebral infarction, patients under chronic aspirin treatment and patients with atrial fibrillation. Urinary 11-dehydro-TXB2, as a major metabolite of TXA2, was measured by radioimmunoassay. The extent of carotid atherosclerosis was determined by B-mode ultrasonography. The mean +/- SD urinary excretion in patients with cerebral infarction and distinct carotid-atherosclerotic lesions (1,725 +/- 239 ng/g creatinine, n = 6) was significantly higher (p less than 0.01) than in healthy subjects (911 +/- 239 ng/g creatinine, n = 44) and patients with cerebral infarction who had no distinct carotid lesion (1,050 +/- 191 ng/g creatinine, n = 6). The urinary excretion of healthy subjects was higher (p less than 0.01) in smokers (1,063 +/- 244 ng/g creatinine, n = 17) than in non-smokers (815 +/- 183 ng/g creatinine, n = 27). Aspirin largely suppressed 11-dehydro-TXB2 excretion (266 +/- 114 ng/g creatinine, n = 7). Three of 5 patients with atrial fibrillation showed very high values. Our results indicated that platelet activation occurs in the atherosclerotic lesions, and that urinary 11-dehydro-TXB2 is the appropriate analytic target for detecting platelet activation.

[Urinary excretion of hydroxyproline in patients with ischemic stroke]. / Wydalanie hydroksyproliny w moczu chorych z niedokrwiennym udarem mózgu.

Urinary excretion of total hydroxyproline being an indicator of the metabolism of systemic collagen was determined in 104 patients with ischaemic stroke and in 45 controls. The determinations were done by the method of Prockop-Udenfried in the urine of patients after 2 days on a non-collagen diet. Increased excretion of hydroxyproline was found in the subgroup of patients with high-grade paresis or paralysis, while in the subgroup with mild paresis these results were normal. The excretion of hydroxyproline in patients with severe paralysis increased during 3-60 days after stroke and then decreased in the period from 60 days to 5 years.

Neurogenic hypertension associated with an excessively high excretion rate of catecholamine metabolites.

A 60 year old hypertensive patient suffered several cerebral infarctions. A phaeochromocytoma was suspected because the excretion rates of vanillylmandelic acid and its methoxy derivatives were raised and the patient had hypertensive crises. No tumour was found, however, by 131mI-iodobenzylguanidine scintigraphy and computed tomography of the abdomen. Moreover, the enhanced orthostatic plasma catecholamine response suggested that the high excretion rates of catecholamine metabolites were more likely to be caused by the syndrome of raised catecholamines after cerebrovascular accidents than a phaeochromocytoma. A phaeochromocytoma should not be diagnosed within several months of cerebral infarction without first excluding the possibility of a hyperadrenergic state induced by cerebral infarction.

Abnormal catecholamine urinary excretion after emotional stimulus in patients with cerebral hemorrhage.

The epinephrine (E) and norepinephrine (NE) urinary excretion before and after a mild "emotional stimulus" (ES) was determined in 22 patients with cerebral infarction and 30 patients with cerebral hemorrhage, as well as in 18 normotensive and 18 hypertensive controls. In patients with cerebral infarction, the majority normotensive, the "emotional stimulus" induced a significant increase in NE excretion, but non-significant alterations in E excretion. Similar changes were noted in normotensive controls. In patients with cerebral hemorrhage, almost all hypertensive, and in hypertensive controls, ES brought about a consistent rise in E excretion without influencing significantly the NE excretion. The presence of a constant increase in E excretion after a mild emotion not only in patients with cerebral hemorrhage but also in subjects with uncomplicated essential hypertension, suggests that the E release found in patients with cerebral hemorrhage is related to the hypertensive state pre-existing the stroke rather than to hemorrhagic stroke itself. The pattern of catecholamine discharge in hypertensive patients might play a part in the occurrence of cerebral hemorrhagic accidents. The epinephrine discharges induce sudden increases in systolic blood pressure which could lead to the rupture of cerebral vessels with hyalinotic or atherosclerotic alterations.

Cyclic AMP concentrations in plasma, cerebrospinal fluid and urine in patients with acute cerebral hemispheric infarction.

Plasmas, cerebrospinal fluid and urine were sampled from 22 patients with cerebral hemispheric infarction and analyzed for cyclic AMP. The following observations were made: (1) In mild cases with slight dysarthria and/or hemiparesis but without disturbance of consciousness (Group I), cyclic AMP in peripheral venous plasma (PVP) remained over the normal lowest level more than 10 days after the onset. Patients with apparent neurological deficits could be divided into two groups. In one group, cyclic AMP in PVP decreased to a subnormal level within about 5 days after the onset of stroke (Group II). In another group (Group III), such a decrease was not observed. Brain isotope scintigrams were revealed negative in Group I. The size of brain infarct as judged by isotope uptake was larger in Group III than in Group II, except for a few cases in which the lesion was restricted in the basal ganglionic region. (2) No clinical significance was, however, found in the time course of cyclic AMP levels in internal jugular venous or femoral arterial plasma, or in cerebrospinal fluid, or of the daily amount of cyclic AMP excretion into urine. (3) Cerebral arterio-venous difference of cyclic AMP was negative in most of the cases.