Low-responders to angiotensin II receptor blockers and genetic polymorphism in angiotensin-converting enzyme.

AIMS: The existence of low-responders to angiotensin II receptor blockers (ARBs) in terms of the preservation of renal function is reported here. We investigated the relationship between the responsiveness to ARBs and insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene. METHODS: The effects of ARBs on proteinuria and the progression of chronic renal failure were examined in 113 patients with chronic kidney disease for 34 months before and 27 months after the addition of ARBs. RESULTS: Although a decrease in blood pressure was seen in the II, DI and DD patient subgroups of the ACE gene, the decrease in proteinuria and the amelioration of loss of renal function were observed in the II and DI but not in the DD patients. Kaplan-Meier analysis was employed with a decrease of the reciprocal of serum creatinine of more than 0.2, the induction of renal replacement therapy or death as endpoints. The analysis comparing the periods before and after the addition of ARBs revealed the extension of time to an end-point by the addition of ARBs in all groups together (II + DI + DD), in Group II, and Group DI but not in the DD patient Group. CONCLUSIONS: These data suggest that DD patients with ACE gene demonstrate diminished response to ARBs in terms of renoprotection and that ACE gene polymorphism needs to be taken into account when using ARBs as a means of renoprotective therapy.

Acute multiple brain infarction in large-artery atherosclerosis is associated with hyperhomocyst(e)inemia.

OBJECTIVES: Although hyperhomocyst(e)inemia had been proven to be a potent risk factor for ischemic stroke, it is still controversial which subtype of stroke is associated with hyperhomocyst(e)inemia. The aim of this study was to clarify the association between plasma homocyst(e)ine (Hcy) levels and stroke subtypes according to TOAST classifications based on MRI findings. METHODS: We prospectively recruited 124 consecutive first-ever ischemic stroke patients hospitalized in Toride Kyodo General Hospital. Each patient underwent brain MRI including diffusion-weighted imaging (DWI) and was evaluated for total plasma Hcy levels in addition to routine laboratory tests. RESULTS: Of the 93 patients enrolled in this study, 19 were subtyped with large-artery atherosclerosis with acute multiple brain infarction [LA-AMBI(+)], 13 with LA-AMBI(-). Patients with LA-AMBI(+) showed significantly higher plasma Hcy levels than those with LA-AMBI(-). Moreover, for LA-AMBI, the plasma Hcy level was associated with an OR of 1.3 (95% CI 1.06-1.71, P=0.017) per 1 mumol increase in concentration, and 1.4 (95% CI 1.04-1.77, P=0.025) after adjustment for age, sex and serum cholesterol levels. CONCLUSION: In the subset of patients with LA strokes, those with high Hcy levels are more likely to have AMBI than those without elevated Hcy levels possibly due to plaque instability.

Risk factors for chronic kidney disease in a community-based population: a 10-year follow-up study.

The purpose of this study was to explore risk factors affecting the incidence of chronic kidney disease (CKD) in general population. We conducted a 10-year follow-up study with 123 764 (male: 41 012, female: 82 752) adults aged 40 years and over who received community-based annual examinations. The primary outcome for the analysis was the development of CKD during the follow-up period. Predictors for the development of CKD were obtained by the significant hazard ratios (HR) in Cox regression model by sex. During the follow-up period, 4307 subjects (male: 2048, female: 2259) developed CKD stage I or II, and 19 411 subjects (male: 4257, female: 15 154) developed CKD stage III or higher. The baseline-adjusted predictor of developing CKD included age, glomerular filtration rate, hematuria, hypertension, diabetes, serum lipids, obesity, smoking status, and consumption of alcohol. Treated diabetes in male subjects, and treated hypertension, systolic blood pressure >160 mm Hg and/or diastolic blood pressure >100 mm Hg, diabetes, and treated diabetes in female subjects were associated with more than a doubling of the HR. For the development of CKD stage III or higher, proteinuria of >or= + +, and proteinuria and hematuria were associated with more than a doubling of the HR in male subjects. The prevalence of newly developed CKD over 10 years was 23 718 subjects (19.2%) in adults. This study suggested that not only hypertension and diabetes but also several metabolic abnormalities were independent risk factors for developing CKD.

Acute disseminated encephalomyelitis following aseptic meningoencephalitis.

A previously healthy 50-year-old man developed aseptic meningoencephalitis with clinical manifestations including fever, headache, seizure, Wernicke aphasia, right hemiplegia, and blindness in the left eye. One and one-half months after remission of meningoencephalitis, marked ataxia and psychiatric symptoms became apparent. Magnetic resonance imaging revealed multiple new lesions involving the basal ganglia, thalamus, white matter, and cerebellum. Despite these developments, cerebrospinal fluid findings continued to improve except for excessive content of myelin basic protein. Within 2 weeks, steroid therapy dramatically resolved the ataxic symptoms and disseminated lesions.

Late escape from the antiproteinuric effect of ace inhibitors in nondiabetic renal disease.

Angiotensin-converting enzyme (ACE) inhibitors exert a renoprotective effect in both diabetic and nondiabetic renal disease with variable efficacy. Proteinuric patients with nondiabetic renal disease, normotension, and restricted protein and sodium intake were treated with ACE inhibitors without diuretics. Fifty-nine patients were treated with either lisinopril (10 mg/d; 36 patients) or enalapril (5 mg/d; 23 patients) over a period of 37.7 +/- 20.7 months. Urinary protein excretion decreased to less than 50% of pretreatment values after 1 to 37 months (6.9 +/- 8.8 months) of therapy in 33 patients (56%); in 29 patients, it reached less than 0.5 g/d of protein. Urinary protein levels remained low in 19 of the 33 patients (57.5%) throughout the entire posttreatment period (30.8 +/- 17.7 months). However, in the remaining 14 patients, escape from the antiproteinuric effect was detected after 19.2 +/- 13.4 months, evidenced by a decrease in the rate of change in creatinine clearance from 0.052 +/- 0.114 mL/min/mon during the low-proteinuria period to -0.697 +/- 1.101 mL/min/mon after the lapse of antiproteinuric effect (P: < 0.001). Although ACE inhibitors reduce the severity of proteinuria in patients with nondiabetic renal disease, our results show that a proportion of patients escape the antiproteinuric effect and subsequently develop an exacerbation of renal dysfunction.

Prevalence of genuine epilepsy among adult emergency patients with an episode of unconsciousness.

OBJECTIVE: Loss of consciousness (LOC) is caused by a variety of conditions including epileptic, cardiac, psychiatric, and autonomic disorders. We investigated the prevalence of presenting attacks of genuine epilepsy among patients of Emergency Department and Department of Cardiology evaluated for an episode of LOC with or without a convulsion. PATIENTS AND METHODS: We retrospectively studied 371 adults presenting to the Emergency Department and Department of Cardiology of our hospital from 1991 to 1999 with a chief complaint of an episode of LOC with or without a convulsion. Ages ranged from 15 to 78 years. Patients were free of severe chronic illnesses, drug abuse, and alcoholism. LOC was considered to represent genuine epilepsy either when the interictal electroencephalogram (EEG) showed epileptiform discharges in the absence of imaging abnormalities, or when both the EEG and imaging studies were unrevealing but one or more previous attacks had occurred and administration of an anticonvulsant prevented subsequent attacks. RESULTS: Patients included 302 patients without a convulsion, and 69 patients with a convulsion. Of the former, 14 subjects had epileptiform discharges on EEG, and three subjects had no epileptiform discharges but had three or four attacks of LOC that were abolished by anticonvulsant therapy. Of the 69 patients with a convulsion, seven had epileptiform discharges, and 12 had two to five attacks, no epileptiform discharges, and a response to anticonvulsant therapy. CONCLUSIONS: The prevalence of presenting attacks of genuine epilepsy in 371 adult patients with an episode of LOC was remarkably high (9.7%: 36 subjects).

Transient QT interval prolongation with inverted T waves indicates myocardial salvage on dual radionuclide single-photon emission computed tomography in acute anterior myocardial infarction.

In patients with acute myocardial infarction (AMI), transient QT interval prolongation with a prominent negative T wave is frequently observed in cases of early spontaneous reperfusion and often indicates a good prognosis. Additionally, in nuclear cardiac imaging, technetium-99m/thallium-201 overlap on dual single-photon emission computed tomography (dual SPECT) in AMI patients indicates the presence of viable myocardium and early recanalization. To elucidate the clinical significance of this transient QT interval prolongation, 34 patients (64 +/- 8 years) admitted within 24h of the onset of anterior AMI were enrolled and classified into 2 groups according to the presence (group A, n=24) or absence (group B, n=10) of scintigraphic overlap on simultaneous dual SPECT imaging. The maximal QTc interval was 0.59 +/- 0.06 s in group A and 0.52 +/- 0.06 s in group B (p<0.01). The peak creatine kinase was lower in group A (2650 +/- 2160 IU/L) than in group B (3490 +/- 2060 IU/L). The left ventricular ejection fraction (LVEF) at discharge was 62 +/- 11% in group A and 49 +/- 14% in group B (p<0.01). The scintigraphic overlap group had a smaller infarct and better LVEF, which suggests that the QT interval prolongation that appears transiently in the acute phase of AMI indicates scintigraphically the presence of salvaged myocardium.

[Feeding methods for long-term bedridden patients with dysphagia under home health care--percutaneous endoscopic gastrostomy (PEG) and intravenous hyperalimentation (IVH)].

We began home health care in our hospital in 1992, and the total number of patients under home health care has reached 380 so far. We report 12 bedridden patients with dysphagia, who have obtained nutrition using two feeding methods. The patients are 7 men and 5 women, with a mean age of 81.4 +/- 8.8 years. The diseases in these patients include cerebrovascular diseases, Parkinson's disease, and senile dementia of the Alzheimer type. The feeding methods include swallowing after swallowing training, percutaneous endoscopic gastrostomy (PEG), and intravenous hyperalimentation (IVH). We have fed these patients by combinating these three methods. The patients fed by swallowing and PEG, swallowing and IVH, and PEG and IVH are five, five and two, respectively. It is very important for bedridden patients to eat and swallow food by themselves, even if the amount is extremely small. Although swallowing training has been performed, the amount of food is not sufficient for life support. Therefore, additional feeding by PEG or IVH is necessary. Sufficient nutrition through a variety of feeding methods is important for patients under home health care.

Urinary tract cancer screening through analysis of urinary red blood cell volume distribution.

BACKGROUND: Hematuria is differentiated between glomerular and urinary tract origins on the basis of urinary red cell morphology. We used this distinction in a program of mass screening for urinary tract cancer to achieve cost-effective and safe hematuria screening. METHODS: Of a total of 21372 adults (mean age 52.3 years; range 20-79 years) participating in a health screening, 912 (4.3%) had a positive dipstick for hematuria and were enrolled in the present study. Urinary red cell volume distribution curves (RDC), the simplest method of assessing urinary red cell morphology, were calculated and subjects were divided into two groups based on their RDC patterns. Group I subjects had a normocytic or mixed pattern and they were immediately investigated for urinary tract malignancy because of the associated risk for urological disease. Group II subjects had a microcytic pattern and, therefore, were judged to be at a low risk of urologic malignancy and were followed up 3 years later without urologic investigations. RESULTS: Among the 38 subjects in group I (4% of all dipstick-positive subjects), one case of bladder cancer was detected. In the remaining 37 patients, 15 cases of benign diseases were discovered. Group II was composed of 869 subjects (96%). The inquiry into their health status conducted 3 years later revealed that 831 (95.6%) were healthy and, of these, 13 had experienced gross hematuria during the period but urological malignancies were ruled out by their urologists, two (0.2%) had died of diseases other than urological cancer and 36 (4.1%) were lost to follow-up. With our method, total costs have been reduced by 93.8% against a conventional setting of a full evaluation for all cases of hematuria. CONCLUSIONS: Microcytic hematuria, accounting for 96% of asymptomatic microhematuria cases in the present study, was not associated with a risk for urinary tract malignancy. Compared with conventional hematuria screening with a complete work-up of all cases of hematuria, investigating only subjects with mixed or normocytic RDC patterns was safe and cost effective.

Pure sensory stroke caused by a cerebral hemorrhage: clinical-radiologic correlations in seven patients.

BACKGROUND AND PURPOSE: Pure sensory stroke (PSS) usually is caused by a lacunar infarct; reports of PSS caused by cerebral hemorrhage have been rare. We correlated clinical and neuroradiologic findings in patients with PSS caused by cerebral hemorrhage. METHODS: We retrospectively studied seven patients with appropriate clinical findings and lesions revealed by X-ray CT and MR imaging (five men, two women; age range, 46-64 years; mean age, 55.9 years). RESULTS: Hemorrhages involved the thalamus, pons, internal capsule, or cerebral cortex. MR imaging revealed thalamic PSS was located in the ventral posterior lateral (VPL) or ventral posterior medial (VPM) nucleus; a lesion producing a thalamic cheiro-oral syndrome was situated on the border between the VPL and VPM. Pontine PSS involved the medial lemniscus together with the ventral trigeminothalamic tract, sparing the anterior and lateral spinothalamic tracts. Accordingly, pontine PSS, but not thalamic PSS, selectively affected vibration and position sense while leaving pinprick and temperature perception intact, and oral sensory involvement was bilateral when cheiro-oral syndrome had a pontine origin. MR imaging revealed hemorrhage in the postcentral gyrus in the cortical variety of PSS and in the posterior part of the posterior limb (thalamocortical sensory pathway) in PSS of internal capsular origin. The postcentral gyral lesion impaired stereognosis and graphesthesia. CONCLUSION: Focal hemorrhages can lead to purely sensory stroke syndromes, and the clinical deficits are fairly well linked with the locations of the bleeds.

Serial positron emission tomography (PET) in gliomatosis cerebri treated with radiotherapy: a case report.

Results of serial positron emission tomography (PET) in a biopsy-proven case of gliomatosis cerebri (GC) are reported. Computed tomography (CT) with and without contrast failed to detect focal abnormalities, but magnetic resonance (MR) revealed iso-intensity or low-intensity lesions in T1-weighted images and high-intensity lesions in T2-weighted images. Lesions were seen in the left thalamus, right temporal lobe and claustrum, and pons. Radiotherapy remarkably improved clinical and imaging findings. Both before and shortly after radiotherapy, 11C-methionine PET images showed hypermetabolism while 15O-water PET images showed a marked increase in cerebral blood flow in GC lesions. However, 6 months later PET images had remarkably improved, appearing nearly normal.

Carotid-cavernous fistula with brainstem congestion mimicking tumor on MRI.

Article abstract-A 65-year-old woman presented with a left abduction deficit and "red eye," mild proptosis, chemosis, arterialization of the conjunctival vessels, intention tremor, and bilateral pyramidal signs. MRI showed significant left-sided brainstem involvement that mimicked a tumor. Right hemiplegia ensued 1 week later. Venous congestion of the brainstem with hemiplegia resulting from shunting of blood flow from both carotid arteries is an extremely rare complication of carotid-cavernous fistula.

Urinary indoxyl sulfate is a clinical factor that affects the progression of renal failure.

We recently demonstrated that indoxyl sulfate is a stimulating factor for the progression of chronic renal failure (CRF). In this study we determined whether the urine or serum levels of indoxyl sulfate are related to the progression rate of CRF in undialyzed uremic patients. Fifty-five CRF patients with a serum creatinine of >2 mg/dl who had not been treated with an oral sorbent (AST-120) were randomly enrolled in the study. We measured the serum and urine levels of indoxyl sulfate, and estimated the recent progression rate of CRF as the slope of the reciprocal serum creatinine versus time (1/S-Cr-time) plot. The mean urinary amount of indoxyl sulfate in the patients was 60 mg/day. Those with indoxyl sulfate urine levels of >60 mg/day had a significantly faster progression rate of CRF than those with <60 mg/day. Especially, those patients with indoxyl sulfate urine levels of >90 mg/day had the highest CRF progression rate and those with indoxyl sulfate urine levels of <30 mg/day had the slowest CRF progression rate. Urinary indoxyl sulfate had a significantly negative correlation with the slope of the 1/S-Cr-time plot. However, the serum level of indoxyl sulfate or the ratio of serum indoxyl sulfate to creatinine was not significantly correlated with the slope of the 1/S-Cr-time plot. In conclusion, high urine levels of indoxyl sulfate are related with a rapid progression of CRF in undialyzed uremic patients. Thus, urinary indoxyl sulfate is one of the clinical factors that affect CRF progression.

Silent lacunar infarction on magnetic resonance imaging (MRI): risk factors.

We investigated the risk factors for silent lacunar infarction and etat criblé detected by magnetic resonance imaging (MRI). Previous reports have evaluated white matter hyperintensities (WMHs) and periventricular hyperintensities (PVHs) on T2-weighted images, but have not distinguished between lacunar infarcts, état criblé, and leukoaraiosis of Binswanger's type. MRI scans were performed in 270 subjects without neurological deficits over the age of 40 years. They were classified into four subtype groups based on MR findings: normal group (n =60), état criblé group (n=69), silent lacunar infarct/PVH(-) group (n=61), and silent lacunar infarct/PVH(+) group (n=80). We examined the following biochemical variables and other potential risk factors by ordinary logistic regression analysis to identify independent and significant risk factors for silent lacunar infarction: serum levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, lipoprotein(a), HbA1c, age, sex, systolic blood pressure, diastolic blood pressure, duration of hypertension, family history, smoking habits, alcohol intake, obesity (body mass index), and atrial fibrillation. Subjects in the silent lacunar infarct/PVH(-) (P<0.01) and PVH(+) (P<0.001) groups were significantly older than normal subjects. The systolic blood pressure was also significantly higher in the silent lacunar infarct/PVH(-) (P<0.04) and PVH(+) (P<0.01) groups compared with the normal group. The duration of hypertension was significantly longer in the silent lacunar infarct/PVH(+) group (P<0.02). There were no significant differences in other risk factors between the normal group and the other groups. Ordinary logistic regression analysis showed that age (chi-square 51.8, P<0.0001) and systolic blood pressure (chi-square 5.7, P<0.02) were significant and independent risk factors for silent lacunar infarction. Aging and hypertension were shown to be independent risk factors for silent lacunar infarction.

Long-term enalapril therapy in patients with chronic renal failure on a low-protein diet. A prospective randomized comparison with metoprolol.

The effect of enalapril (5-10 mg/day) on the progression of chronic renal failure (CRF) was compared with that of metoprolol (40-120 mg/day) in 28 patients for 24 months in a prospective study. Throughout the study, there was no significant difference between the 2 groups in protein intake and urinary sodium excretion. But there was a significant difference between the 2 groups in diastolic and mean arterial blood pressure at 6 months. In the serum creatinine level, there was a significant difference between the 2 groups at 6, 12, 18, and 24 months. In creatinine clearance, there was a significant difference between the 2 groups at 24 months. In addition, the progression of CRF was significantly faster in the metoprolol group than the enalapril group as estimated from the slope of creatinine clearance (p < 0.05) and the slope of glomerular filtration rate (p < 0.0005). In urinary protein excretion, there was a significant difference between the 2 groups at 6 and 18 months (p < 0.05). These findings indicate that enalapril has a suppressive effect on the progression of CRF and also has an antiproteinuric effect by a mechanism independent of its antihypertensive effect.

Subclinical cerebral lesion accumulation on serial magnetic resonance imaging (MRI) in patients with hypertension: risk factors.

OBJECTIVES: We investigated the occurrence in hypertensive patients of new subclinical changes in the brain by serial magnetic resonance imaging (MRI). METHODS: MRI was performed serially in 98 hypertensive subjects without neurologic deficits at least once a year for 3 years. All received antihypertensive medicines Blood pressure, serum lipids, diabetes mellitus, body mass index (BMI), and other clinical factors were correlated with results. RESULTS: Seventy-nine patients had unchanged MRI findings, while 19 developed new lesions (silent lacunar infarct and etat criblé in 3, silent lacunar infarct in 9, and etat criblé in 7). Follow-up systolic blood pressures were significantly higher than individual baselines in the unchanged group, while the follow-up diastolic blood pressures in the new lesion group were significantly lower than in the unchanged group. BMI was significantly lower in the new lesion group. Follow-up HbA1c levels in both groups were significantly higher than at baseline. Diabetes mellitus was significantly more frequent in the new lesion group than in the unchanged group. No significant differences were apparent in serum lipids level, prescribed antihypertensive medications, and other potential risk factors. CONCLUSIONS: New subclinical MRI changes in hypertensive subjects occurred relatively frequently (19 of 98 subjects, or 19.4%). An excessive fall in diastolic blood pressure, diabetes mellitus, and low BMI emerged as candidate risk factors for these changes.

Paradoxical hyperfixation of hexamethylpropyleneamine oxime in cerebral infarction.

We describe four patients with cerebral infarction and 99mTc-hexamethylpropyleneamine oxime (HMPAO) hyperfixation in distributions corresponding to the infarctions seen at CT and/or MR imaging. Increased HMPAO extraction due to hyperpermeability across the blood-brain barrier and increased retention due to reduced back diffusion of the tracer probably accounted for the increased fractional fixation in infarcts seen in our patients.

Quasi-steadiness approximation for the two-compartment solute kinetic model.

We analytically solved the equation of the variable volume, two-compartment solute kinetic model (TCSKM). From the solution, we constructed an expression of weekly concentration profiles developing in the patient's body by routine hemodialyses. Obtained formulas can be used to calculate Kt/V, solute reduction index (SRI), the solute generation rate (G) per unit distribution volume (V), and a mass transfer coefficient (MTC) between the two compartments. To estimate these parameters, the formulas only need three-point data during a dialysis, that is, pre-, one-hour, and post-dialysis solute concentrations instead of four that would otherwise be needed. A 48 hour data point is not required. The weekly concentration profiles can be easily calculated by the formulas. As examples of clinical applications, we calculated Kt/V, G/V, and SRI of urea, Cr, and uric acid using plasma data of 121 hemodialyzed patients. Then the results were compared with the single-compartment solute kinetic model (SCSKM). The obtained mean MTC/V values, that is, 1.08 (1/hr) for urea, 0.53 (1/hr) for Cr, and 1.11 (1/hr) for uric acid, were consistent with the previous works. SCSKM overestimated the mean G/V by 7.1%, 15.9%, and 10.0%, and the mean SRI by 6.7%, 18.6%, and 10.0%, for urea, Cr, and uric acid, respectively. The solute distribution volume ratio of TCSKM to SCSKM, (V)TCSKM/(V)SCSKM, depended on the value of MTC/V and the hemodialysis duration. Using pedometers, we measured the total number of steps the patients took during a week. We found that the total number of steps in a week was significantly correlated with the Cr generation rate (r = 0.285, P < 0.03), but that it was not significantly correlated with the other generation rates (r = 0.204, P > 0.09 for urea, and r = 0.209, P > 0.08 for uric acid). These data suggest that the Cr generation rate is related to the patient's physical activity. We conclude that the formulas can estimate an adequate dialysis prescription for the hemodialyzed patient.