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Biomedical subjects

M Shindo

Publications and source records attributed to M Shindo.

At least 19 recordsLinked to original sources

Failure to detect vertical transmission of hepatitis C virus.

OBJECTIVE: To search for transmission of hepatitis C virus (HCV) from infected mothers to their infants. DESIGN: Prospective clinical, serologic, and molecular biologic follow-up (at least 3 months) of the infants of mothers with anti-HCV antibody. SETTING: A county hospital providing primary and referral care in high-risk obstetrics (perinatology). PATIENTS: Twenty-three mothers with anti-HCV antibody and their 24 infants. METHODS: An enzyme-linked immunosorbent assay (EIA) and a four-antigen recombinant immunoblot assay (RIBA) were used to test for anti-HCV antibody; serum HCV RNA was measured in two independent laboratories by reverse transcription and polymerase chain reaction (PCR) using nested primers in the 5'-noncoding region. Infant samples were tested for HCV RNA by PCR at delivery and after 3 to 6 months of follow-up. Each sample was tested at least four times in two independent laboratories. RESULTS: Twenty-nine of 648 mothers (4.5%; 95% Cl, 3.0% to 6.4%) had anti-HCV antibody; these women had 30 babies. Twenty-three mothers and their 24 babies were followed at least 3 months (mean follow-up, 52 weeks). Of the 23 mothers, 21 (91%; Cl, 72% to 99%) had a reactive RIBA; one woman had an indeterminate RIBA and was positive for HCV RNA by PCR. In 16 of 23 mothers (70%; Cl, 47% to 87%), PCR yielded a positive result in both laboratories. The mean maternal alanine aminotransferase (ALT) level was 1.6 times the normal value. All the babies had anti-HCV antibody in cord-blood samples, but antibody disappeared or diminished in strength in interval samples, and no infant had evidence of active production of anti-HCV antibody. Only 1 of 24 (4%; Cl, 0.1% to 21%) cord-blood samples was HCV RNA positive, and none of 24 (0%; Cl, 0% to 14%) follow-up samples was positive for HCV RNA by PCR in either laboratory. Four mothers and one baby had antibody to HIV. CONCLUSIONS: Infant anti-HCV antibody is most likely acquired passively in utero, and vertical transmission of HCV is uncommon.

Female

[Clinical evaluation of lumbosacral nerve root and lateral stenosis using coronal MR imaging].

MR imaging is being used more frequently to study the lumbar spine and is becoming the modality of choice in the assessment of patient with low back pain. Using a new technique of coronal and half coronal scan with MR imaging, it was possible to visualize L4, L5 and S1 nerve roots accurately. We described the MR findings of lateral stenosis using this technique. Several characteristic MR findings were identified, and the most important one was nerve root impingement in the intervertebral foramen. We consider that coronal and half coronal scan with MR imaging is useful in diagnosis of lateral stenosis.

Adult

Sensitivity of serological assays to identify blood donors with hepatitis C viraemia.

Blood donors at high risk of hepatitis C virus (HCV) infection were tested for viraemia by the polymerase chain reaction (PCR). PCR results were accepted as positive only if reactive in 3 of 4 tests and if confirmed in an independent laboratory. The sera were also tested by 6 different assays to determine the ability of current serological assays to detect viraemic blood donors. Of 19 PCR-positive sera, only 13 (68%) were detected by the most sensitive of the serological assays. If these results are confirmed, automated PCR assays may be required for blood-donor screening to prevent transmission of HCV.

Blood Donors

Long-term follow-up of patients with chronic hepatitis C treated with alpha-interferon.

We reanalyzed the results of a pilot study of recombinant alpha-interferon therapy for chronic non-A, non-B hepatitis in light of the recent discovery of the hepatitis C virus and the development of diagnostic assays for this agent. Stored serum samples from 10 patients treated between 1984 and 1986 were tested for antibody to hepatitis C virus and hepatitis C virus RNA before, during and after therapy. In addition, the current clinical, serum biochemical and virological statuses of these patients were evaluated to determine the long-term effects of interferon therapy. All patients had evidence of hepatitis C virus infection, with hepatitis C viral RNA, antibody to hepatitis C virus or both markers detectable in serum. Serum hepatitis C virus RNA was found to disappear in seven of eight patients whose aminotransferase levels became normal with interferon therapy but remained present in two patients who did not respond to therapy. Levels of hepatitis C virus RNA decreased and disappeared when serum aminotransferases fell to normal levels but rose with subsequent elevation of aminotransferase levels in two patients who had relapses in disease when interferon was stopped. During a follow-up of 3 to 6 yr, hepatitis C virus RNA remained undetectable in the six patients whose serum aminotransferase levels remained normal after interferon therapy. However, neither initial titers of hepatitis C virus RNA nor disappearance of viral RNA from serum during treatment predicted a sustained response. Thus long-term beneficial responses to alpha-interferon can occur in patients with chronic hepatitis C and are associated with sustained loss of hepatitis C virus RNA from serum.

Chronic Disease

A pilot study of ribavirin therapy for chronic hepatitis C.

Interferon-alpha therapy is of proven efficacy in chronic hepatitis C, but it is not universally effective and may be associated with intolerable side effects. Ribavirin is a nucleoside analog with a broad spectrum of antiviral action. We conducted an uncontrolled pilot study of ribavirin therapy in 13 patients with chronic hepatitis C. Ribavirin was given for 6 mo, in a dose that was increased, at 2-mo intervals, from 600 mg to 1,000 mg to 1,200 mg/day. Serum ALT levels gradually decreased in all 13 treated patients; the mean percentage of decrease was 67% (from 210 U/L [range = 109 to 593] to 63 U/L [range = 22 to 108 U/L]; p = 0.0006) after 6 mo of treatment. Serum aminotransferase levels fell to the normal range in four patients (31%). In the 3 to 6 mo after cessation of ribavirin therapy, serum aminotransferase activities gradually rose to near pretreatment levels in all but one patient. Therapy was associated with a significant decrease in the geometric mean titer of hepatitis C virus RNA in serum (1:1,981 vs. 1:199; p less than 0.02) although no patients lost hepatitis C virus RNA from serum during therapy. No significant improvement was seen in liver histological appearance. Ribavirin therapy resulted in mild, reversible hemolysis; no patient exhibited symptomatic anemia. These findings suggest that ribavirin has a beneficial effect in patients with chronic hepatitis C, although further studies are needed to determine how ribavirin is best used.

Adult

Administration of slow-release nifedipine does not affect lactate threshold, hormone release during exercise, and quality of life in normal subjects.

In a double-blind crossover study of 10 normal healthy subjects, we examined the effects of slow-release nifedipine (nifedipine-SR, 10 mg b.i.d) administration on exercise capacity, hormone levels during exercise, and quality of life (QOL) after a 2-week treatment. Two exercise tests, a progressive exercise test and a constant work-rate exercise test, were performed. Maximal oxygen uptake (VO2max) and blood lactate concentration were measured during the progressive exercise test and the exercise intensity corresponding to half lactate threshold (LT), LT, and 4 mmol/l of lactate concentration was determined. Subjects underwent 20 minutes of constant work-rate exercise at each work load, and blood lactate, plasma epinephrine, plasma norepinephrine, plasma renin activity, plasma aldosterone, atrial natriuretic peptide, plasma beta-endorphin, and met-enkephalin were measured. Taking nifedipine-SR had no effect on the responses of blood pressure, heart rate, VO2max, maximal work load, and LT compared to taking placebo. Blood lactate, plasma catecholamine, plasma renin activity, aldosterone, atrial natriuretic peptide, and beta-endorphin levels increased during exercise, and there was no difference between nifedipine-SR and placebo. Met-enkephalin did not increase with either treatment. In the QOL questionnaires, no differences were noted between the two treatments. These findings suggest nifedipine-SR to be a potentially useful drug in view of the lack of effect on exercise capacity, hormone release, and QOL.

Adolescent

Effects of arotinolol on exercise capacity and humoral factors during exercise in normal subjects.

A placebo-controlled, double-blind crossover study was undertaken in 10 normal subjects to examine the effects of arotinolol (10 mg bid), a nonselective beta blocker with alpha-blocking activity, on exercise capacity and hormone levels during exercise after a 2-week treatment period. Maximal oxygen uptake (VO2 max) and blood lactic acid concentration (LA) were measured during progressive exercise testing. An exercise intensity equivalent to 4 mmol/l of LA was used for the constant workload exercise test. Humoral factors were measured after 20 minutes of constant workload exercise. The administration of arotinolol significantly decreased systolic blood pressure and heart rate at rest and during exercise, but diastolic blood pressure did not change. No significant difference was found between arotinolol and placebo with regard to VO2 max and maximal workload. Plasma renin activity (PRA), aldosterone (PAC), and norepinephrine (NE) levels at rest and during exercise did not differ between the two treatments. In contrast, plasma epinephrine (EN) levels at rest and during exercise were significantly greater with arotinolol. Atrial natriuretic peptide (ANP) at rest did not differ between the two treatments. However, exercise caused a significant increase in ANP after arotinolol treatment. These findings suggest that arotinolol decreases blood pressure and heart rate without affecting exercise capacity.

Adrenergic beta-Antagonists

Active and inactive renin after exercise.

The effects of graded exercise on plasma concentrations of active and inactive renin were studied in seven healthy men. Exercise was performed on a cycle ergometer at four different exercise intensities (corresponding to 30%, 50%, 80% and 87% of VO2max) for 10 min each. Concentrations of active renin and total renin after activation by trypsin were measured by direct immunoradiometric assay. Non-trypsin-activated renin concentration (inactive) was obtained by subtraction. Active renin concentrations at 30%, 50%, 80% and 87% of VO2max were 1.2, 1.9, 3.1 and 4.6 times higher than the control concentration, respectively. Similar increases in plasma renin concentration, determined by conventional enzymatic assay, were observed at every stage. In contrast, changes in inactive renin concentration were not significant at any stage. Significant increases in noradrenaline concentration were found at every exercise stage, but adrenaline, aldosterone and lactate concentrations were significantly elevated only after exercise at 50%, 80% and 87% of VO2max. The similarity between the changes in concentration of active renin and noradrenaline would suggest that sympathetic nerve activity may have been responsible either for the release of active renin or for the conversion of inactive renin to its active form in the kidney.

Adult

Pure word deafness due to left hemisphere damage.

We report the case of a 55 year-old right-handed man who presented with a long lasting pure word deafness following left thalamic bleeding. There was no sign of aphasia. The auditory deficit was specific for language, while recognition of music and environmental sounds was normal. CT, MRI and PET examinations showed that the lesion was anatomically and functionally confined to the left cerebral hemisphere, mainly the white matter of the temporal and parietal lobes. Wernicke's area was largely preserved. It is proposed that pure word deafness was consequent to the isolation of Wernicke's area from incoming auditory information due to the interruption both of the association fibers from the right auditory area traveling across the corpus callosum and of the left auditory radiations.

Brain Injuries

Hepatitis C virus replication during acute infection in the chimpanzee.

The events following experimental infection of 2 chimpanzees with the H strain of hepatitis C virus (HCV) were studied by quantitating the levels of HCV RNA in liver and serum. Serum and liver samples were tested every 1-3 weeks for up to 32 weeks. The genomic and antigenomic strands of HCV RNA were individually detected in liver and serum by strand-specific reverse transcription followed by polymerase chain reaction (PCR) using nested primers specific for the 5' noncoding region of the HCV genome and were quantitated by end-point dilution of the nucleic acid extract. Both genomic and antigenomic strands were detected in liver and serum within 1 week after inoculation and approximately 1 week before the development of elevated levels of alanine aminotransferase (ALT) activity. Changes in levels of antigenomic strand paralleled those of the genomic strand in both serum and liver. Titers of HCV RNA in serum and liver generally correlated with changes in ALT levels.

Acute Disease

Influence of workload on the antihypertensive effect of exercise.

1. The relation between workload and the antihypertensive effect of exercise therapy in hypertensive patients, and the mechanism of that effect, were investigated. 2. Twenty-six patients participated in the study and were randomly assigned to 10 weeks of either low or high workload exercise. In the low workload group, 16 mild hypertensive patients were treated with bicycle ergometer exercise at approximately 50% of their maximum oxygen consumption (VO2max) for 60 min three times a week for 10 weeks. In the high workload group, 10 mild hypertensive patients exercised on the same schedule, but at approximately 75% of VO2max. 3. After 10 weeks of exercise, the low workload group had significantly lower systolic (9 mmHg), mean (6 mmHg) and diastolic (6 mmHg) blood pressures. In the high workload group, decreases in systolic (3 mmHg), mean (4 mmHg) and diastolic (5 mmHg) blood pressure were not statistically significant. 4. In the low workload group, changes in haemodynamic and humoral variables were not significant, except for a reduction in plasma norepinephrine at week 7. Cardiac index and plasma norepinephrine tended to decrease. In the high workload group, plasma norepinephrine and the renin-angiotensin system were transiently stimulated after 4 weeks of exercise. Stroke volume significantly increased (+26.4%) after 10 weeks of high workload exercise. 5. Based on these results and better patient compliance with the exercise programme in the low workload group than in the high workload group, low workload exercise therapy was recommended to mild hypertensive patients.

Adult

Mild exercise decreases plasma endogenous digitalislike substance in hypertensive individuals.

Changes in a plasma endogenous digitalislike substance were investigated in relation to the antihypertensive mechanism of mild exercise. Fifteen women with mild essential hypertension and seven normotensive female volunteers were divided into exercised hypertensive (n = 10), nonexercised hypertensive (n = 5), and nonexercised normotensive (n = 7) groups. A 4-week general clinical observation period preceded the study period of 10 weeks. The exercised hypertensive individuals were treated with a lactate threshold exercise that corresponded to approximately 50% of the maximum oxygen consumption three times a week, whereas the nonexercised groups were observed at the outpatient clinic as control groups. In the exercised group, systolic blood pressure fell by 7 mm Hg (p = 0.05), diastolic by 6 mm Hg (p less than 0.01), and mean blood pressure by 7 mm Hg (p less than 0.01) after 10 weeks. The reduction in the plasma endogenous digitalislike substance was significant after 7 (-1.02 ng/ml, p less than 0.05) and 10 (-1.04 ng/ml, p less than 0.05) weeks in this group. It positively correlated with the reduction in diastolic (r = 0.70, p less than 0.05) or mean (r = 0.66, p less than 0.05) blood pressure and with changes in plasma norepinephrine (r = 0.76, p less than 0.05). The mean corpuscular volume of erythrocytes decreased (-1.7 fl, p less than 0.01) after 10 weeks of exercise, and the plasma volume index tended to decrease (-108 ml/m2, p = 0.28). In the control groups, significant changes in blood pressure and plasma endogenous digitalislike substance were not observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure

The benefits of the low intensity training.

This presentation addressed the researches concerning the effects of the low intensity training on health promotion done in our laboratory. Supervised physical training performed at 50% VO2max or lactate threshold for 60 minutes, 3 or 5 times a week for 30 sessions could induce the improvement in VO2max, lipid profiles, and augment in cardio-pulmonary baroreflex. This training was also applied for patients in ischemic heart disease, hypertension, and obesity. These patients could improve their aerobic work capacity. Hypertensive patients could reduce their blood pressure in association with modulating in humoral factors without changes in body weight and diet. The obese patients succeeded in significant body reduction with mild food reduction. We also found the existence of break-point of double product (BPDP) during graded exercise test corresponding to lactate threshold. BPDP will be able to use for estimating lactate threshold. This low intensity training, which is easier and safer, can be recommended to the wide-variety of persons including older person to promote health.

Coronary Disease

Dependence of endocochlear potential on basolateral Na+ and Cl- concentration: a study using vascular and perilymph perfusion.

Inside-positive endocochlear potential (EP) and high potassium concentration in the endocochlear duct are generated by transepithelial K+ transport in marginal cells of the stria vascularis. In order to estimate the degree of involvement of Na+ and Cl- in K+ transport in marginal cells, EP in guinea pigs was measured under artificial vascular and perilymphatic perfusion in situ. Na+ depletion due to both vascular and perilymphatic perfusion decreased EP by -10.0 +/- 4.1 mV (delta EP = -86 +/- 5.2 mV, n = 5) from the control value of 78 +/- 4.3 mV (p < 0.01). Cl- depletion due to vascular and perilymphatic perfusion also decreased EP by -10.0 +/- 4.9 mV (delta EP = 8.5 +/- 4.8 mV, n = 6) from the control value of 77 +/- 5.1 mV (p < 0.01). However, under either vascular or perilymphatic perfusion, even lowering of Na+ or Cl- concentration in the perfusate decreased EP only slightly compared to the results under both vascular and perilymphatic perfusion. Furosemide, a blocker of Na+/K+/2Cl- symport, decreased EP under vascular perfusion. This dependency of EP on basolateral Na+ and Cl- concentration strongly suggests that K+ transport by the marginal cell is dependent on the basolateral Na+ and Cl- concentration, and that Na+/K+/2Cl- symport is raised as a possible mechanism for Na+ and Cl- dependency of EP.

Animals

Absence of hepatitis C viral RNA from saliva and semen of patients with chronic hepatitis C.

Body fluids from 14 patients with chronic hepatitis C were analyzed for the presence of hepatitis C viral RNA using the polymerase chain reaction. Nucleic acids were extracted from serum, saliva, and semen in guanidinium thiocyanate, subjected to reverse transcription, and then amplified by a double polymerase chain reaction technique using "nested" primers from the highly conserved 5' non-coding region of the hepatitis C virus genome. Hepatitis C viral RNA was found in the serum of all patients in titers ranging between 10(-1) and 10(-3). The hepatitis C viral genome was not detected in any saliva or semen sample. These findings suggest that body fluids of patients with chronic hepatitis C are rarely, if ever, contaminated with the hepatitis C virus. This may help to explain the infrequent transmission of this disease by sexual or close physical contact.

Adult

Viable myocardium identified by reinjection thallium-201 imaging: comparison with regional wall motion and metabolic activity on FDG-PET.

Reinjection thallium-201 scans were performed in 68 patients with coronary artery disease after the routine stress-delayed scans for more accurate identification of new fill-in. Following the stress and 3 hour delayed thallium-201 SPECT scans, 40 MBq (1.1 mCi) was injected at rest, and 10 min later, the reinjection SPECT scan was obtained. To determine whether the reinjection method can aid in identifying ischemic but viable myocardium, the thallium-201 findings were compared with regional wall motion on radionuclide ventriculography in 61 patients and with metabolic activity on positron emission tomography (PET) using F-18 fluorodeoxyglucose (FDG) in 18 patients. The reinjection scan identified new fill-in which had not been shown on the stress-delayed scans in 6 of the 22 patients (27%) or in 29 of the 105 segments (28%). Regional wall motion was preserved more in the segments that exhibited new fill-in after reinjection (wall motion score = 1.64 +/- 1.29) than in those without new fill-in (score = 2.72 +/- 1.04) (p < 0.01). In the comparative study with FDG-PET, persistent FDG uptake was observed in all segments with new fill-in (20/20 segments: 100%); whereas, it was seen in only 7 of the 28 segments (25%) without new fill-in after reinjection (p < 0.05). We concluded that the segments having new fill-in after reinjection may represent ischemic but viable myocardium. Thus, the reinjection thallium-201 scan should be performed to identify ischemic myocardium which occasionally cannot be detected by the routine stress-delayed thallium-201 scans.

Adult

Plasma exudation by activated plasma kallikrein after intraperitoneal injection of lambda-carrageenin or endotoxin in rats.

The experimental study was carried out to examine whether intraperitoneal injection of carrageenin or endotoxin activates plasma kallikrein-kinin system to induce plasma exudation in rats. Intraperitoneal injection of 2% lambda-carrageenin induced plasma exudation in the peritoneal cavity by activation of plasma prekallikrein. Intraperitoneal injection of endotoxin (3mg/kg) also resulted in intraperitoneal plasma exudation, but plasma kallikrein-kinin system did not seem to be involved.

Animals